JP6830256B2 - How to prepare polyrotaxane and polyrotaxane - Google Patents

Description

Field of Invention The present invention relates to a method for preparing a polyrotaxane and a polyrotaxane that can be prepared by using such a method. Furthermore, the present invention relates to a method for preparing a crosslinked polyrotaxane and a crosslinked polyrotaxane that can be prepared using such a method. The present invention also relates to products containing polyrotaxane or crosslinked polyrotaxane, or products that can be prepared from polyrotaxane or crosslinked polyrotaxane. The present invention further relates to the use of polyrotaxane or crosslinked polyrotaxane in a variety of applications.

Background of the Invention Polyrotaxane has become a material of great interest for industrial applications, for example, as a material for paints and adhesives.

Polyrotaxane is a supramolecular assembly containing a cyclic molecule and a polymer. In polyrotaxane, the cyclic molecule is penetrated by a polymer, where the polymer penetrates the opening of the cyclic molecule.

A known synthetic approach for obtaining polyrotaxane involves first providing a polymer that has been synthesized prior to forming polyrotaxane. The polymer is then mixed with the cyclic molecule and the cyclic molecule is penetrated by the polymer chain. In order to prevent the penetrated cyclic molecule from desorbing from the polymer chain, blocking groups that prevent the cyclic molecule from desorbing from the polymer chain and thus the polyrotaxane from decomposing are provided at both ends of the polymer chain. Need to be placed.

U.S. Pat. No. 7,943,718 B2 discloses a method of forming polyrotaxane, in which poly (ethylene glycol) is mixed with cyclodextrin. Cyclodextrin is then penetrated by a poly (ethylene glycol) chain to form an inclusion complex, which is recovered from the reaction mixture. In the next step, the inclusion complex is dispersed in the reaction medium and adamantyl groups are attached to both ends of the poly (ethylene glycol) chain. Since the adamantyl groups are sterically large interfering groups, these groups prevent cyclodextrin from desorbing from the poly (ethylene glycol) chain.

While poly (ethylene glycol) is a hydrophilic polymer, it remains difficult to pass cyclodextrin over hydrophobic polymer chains such as polyisoprene or polybutadiene. In addition, the synthesis disclosed in US 7 943 718 B2 requires that the attachment of steric interfering groups that prevent cyclic molecules from detaching from the polymer chain is carried out in a separate step. .. This complicates the synthesis protocol.

Therefore, there is a need to provide additional methods for preparing polyrotaxanes that are easily implemented and widely applicable, as well as additional polyrotaxans.

Description of the Invention This requirement is addressed by the present invention as defined in the claims, as described herein, and as described in Examples and Drawings.

The present invention is a method of preparing polyrotaxane:
A step of performing radical copolymerization of at least (a) one first polymerizable monomer having one stopper group and at least (b) one second polymerizable monomer, wherein the second monomer is used. Includes steps in which is copolymerized by cyclic molecules;
During the copolymerization, a copolymer penetrating the cyclic molecule is formed, and during the copolymerization, the first monomer having a stopper group is incorporated at least partially between both ends of the chain of the copolymer. Moreover, the stopper group prevents the cyclic molecule from decomposing from the copolymer; and the amount of the first monomer having a stopper group is 0.1 mol% to 20 mol based on 100 mol% of the total amount of the polymerizable monomer. The amount of%, regarding the method.

In certain embodiments of the method of preparing the polyrotaxane of the present invention, the method is described below:
(A) A step of providing a composition containing a cyclic molecule and a first polymerizable monomer having a stopper group;
(B) A step of combining the second polymerizable monomer with the composition of the step (a) and a step of forming a complex of the cyclic molecule and the second monomer; and (c) the composition of the step (b). Including the step of performing radical copolymerization with respect to form a polyrotaxane;
During the copolymerization, a random copolymer penetrating the cyclic molecule is formed, and during the copolymerization, the first monomer having a stopper group is randomly incorporated along the chain of the copolymer.

In another embodiment of the method of preparing the polyrotaxane of the present invention, the method is described below:
(A) A step of providing a composition containing a cyclic molecule and a second polymerizable monomer;
(B) In the step of performing radical polymerization on the composition of step (a) using a bifunctional radical initiator to form block B containing a repeating unit derived from the second monomer. A step in which the second monomer is complexed with a cyclic molecule;
(C) A step of combining the first polymerizable monomer having a stopper group with the block B; and (d) radical copolymerizing the first polymerizable monomer on both ends of the block B to derive from the first monomer. The step of forming the block A at both ends of the block B including the repeating unit to be formed is included.
During the copolymerization, an ABA block copolymer is formed, the cyclic molecule is passed over block B, and block B is placed between the two blocks A.

In another embodiment of the method of preparing the polyrotaxane of the present invention, the method is described below:
(A) A step of providing a composition containing a first polymerizable monomer having a stopper group;
(B) A step of radically polymerizing the composition of step (a) in the presence of a bifunctional chain transfer agent to form block A containing a repeating unit derived from the first monomer;
(C) The step of combining the second polymerizable monomer with the block A; and (d) the second polymerizable monomer is radically copolymerized with the block A and inserted into the block A and derived from the second monomer. A step of forming a block B containing a repeating unit, comprising a step of copolymerizing the second monomer with a cyclic molecule;
During the copolymerization, an ABA block copolymer is formed, the cyclic molecule is passed over block B, and block B is placed between both blocks A.

In yet another embodiment of the method of preparing the polyrotaxane of the present invention, the method is described below:
(A) A step of providing a composition containing a first polymerizable monomer having a stopper group;
(B) A step of performing radical polymerization on the composition of step (a) to form a block A containing a repeating unit derived from the first monomer having a stopper group;
(C) A step of radically copolymerizing the second polymerizable monomer with the block A to form a block B containing a repeating unit derived from the second polymerizable monomer attached to the block A. The second monomer is complexed with the cyclic molecule; and (d) the third polymerizable monomer having a stopper group is radically copolymerized with the block B to form the block C. Includes steps in which the third monomer is the same as or different from the first monomer;
During the copolymerization, an ABC block copolymer is formed, the cyclic molecule is passed over block B, and block B is placed between block A and block C; and said first having a stopper group. The amount of the combination of one monomer and the third monomer is 0.1 mol% to 20 mol% based on the total amount of the polymerizable monomer of 100 mol%.

The present invention is also a polyrotaxane comprising one cyclic molecule and one copolymer penetrating the cyclic molecule, wherein the copolymer is from one first polymerizable monomer having at least (a) one stopper group. A nonionic copolymer comprising a derived structural unit and at least (b) a structural unit derived from one second polymerizable monomer, wherein the structural unit derived from the first monomer having a stopper group is The structure, which is at least partially incorporated between both ends of the chain of the copolymer, prevents the cyclic compound from decomposing from the copolymer and is derived from the first monomer having a stopper group. With respect to polyrotaxane, the amount of the unit is 0.1 mol% to 20 mol% with respect to the total amount of structural units of the copolymer of 100 mol%.

In one embodiment of the polyrotaxane of the invention, the polyrotaxane can or is obtained by any one of the methods of the invention described herein.

In one embodiment of the polyrotaxane of the present invention, the copolymer is such that the structural unit derived from the first polymerizable monomer having a stopper group is at least partially between both ends along the chain of the copolymer. It is a random copolymer incorporated at random.

In another embodiment of the polyrotaxane of the present invention, the copolymer comprises a block A comprising a repeating unit derived from the first polymerizable monomer having a stopper group and a repeating derived from the second polymerizable monomer. A block copolymer comprising a block B containing a unit and a block C containing a repeating unit derived from a third polymerizable monomer, wherein the repeating unit derived from the third monomer is the first. Same or different from the repeating unit derived from the monomer, in the block copolymer, the block B is placed between the block A and the block C, the cyclic molecule is passed over the block B, and the The amount of the combination of the structural unit derived from the first monomer and the structural unit derived from the third monomer is 0.1 mol% to 20 mol% based on the total amount of 100 mol% of the structural units of the copolymer. There is a block copolymer.

The present invention further comprises a method of preparing a crosslinked polyrotaxane, which is (a) a step of providing the polyrotaxane as described herein and (b) chemically or physically crosslinking the polyrotaxane. It relates to a method including a step.

Accordingly, the present invention also relates to a crosslinked polyrotaxane in which any of the polyrotaxans described herein are chemically or physically crosslinked.

The present invention also relates to the use of the polyrotaxanes described herein or the crosslinked polyrotaxans as self-healing materials.

The present invention further relates to the use of the polyrotaxanes described herein or crosslinked polyrotaxans for encapsulation, eg, encapsulation of pharmaceutically active agents.

The present invention also relates to the use of the polyrotaxanes described herein or the crosslinked polyrotaxans as carriers for pharmaceutically active agents.

The present invention further relates to a method of coating the surface with polyrotaxane, which comprises coating the surface with a solution or dispersion containing the polyrotaxane described herein.

The present invention also relates to the use of the crosslinked polyrotaxane described herein as an adhesive.

The present invention further relates to a dispersion composed of metal particles and / or metal oxide particles and the polyrotaxane described herein.

The present invention also relates to a complex composed of metal particles and / or metal oxide particles and the polyrotaxane described herein.

It is a schematic representation of polyrotaxane which concerns on embodiment of this invention. It is the formation of the ring gel and the schematic representation of the ring gel which concerns on embodiment of this invention. ¹ H NMR spectrum of a) polyrotaxane according to Example 2 of the present invention and b) a free copolymer obtained by hydrolysis of polyrotaxane prepared as described in Example 2 is shown. The ROESY NMR spectrum of the polyrotaxane according to the examples of the present invention showing that the cyclodextrin derivative is passed over the copolymer is shown. The DOSY NMR spectrum of the polyrotaxane according to the examples of the present invention showing that cyclodextrin is passed over the copolymer is shown. The isothermal titration calorimetry curve of the polyrotaxane according to the examples of the present invention showing that free cyclodextrin is almost absent in the sample is shown. The optical absorption spectra of the Nile Red dye in the presence of a) and b) of the polyrotaxane according to the examples of the present invention are shown. An electron micrograph of spherical micelle aggregates formed in an aqueous solution from polyrotaxane according to an example of the present invention is shown. It is a graph display of the uptake of the drug by the solution of polyrotaxane which concerns on Example of this invention. The ¹ H NMR spectrum of the polyrotaxan according to the Example of this invention is shown. The ¹ H NMR spectrum of the polyrotaxan according to the Example of this invention is shown. The ¹ H NMR spectrum of the polyrotaxan according to the Example of this invention is shown. The ¹ H NMR spectrum of the polyrotaxan according to the Example of this invention is shown.

Detailed Description of the Invention An object of the present invention has been to provide an additional method for preparing a polyrotaxane that is easily practiced and widely applicable.

Therefore, the present invention is a method for preparing polyrotaxane:
A step of performing radical copolymerization of at least (a) one first polymerizable monomer having one stopper group and at least (b) one second polymerizable monomer, wherein the second monomer is used. Includes steps in which is copolymerized by cyclic molecules;
During the copolymerization, a copolymer penetrating the cyclic molecule is formed, and during the copolymerization, the first monomer having a stopper group is incorporated at least partially between both ends of the chain of the copolymer. Moreover, the stopper group prevents the cyclic molecule from decomposing from the copolymer; and the amount of the first monomer having a stopper group is 0.1 mol% to 20 mol based on 100 mol% of the total amount of the polymerizable monomer. The amount of%, regarding the method.

Throughout this specification, as used herein, the term "polyrotaxane" refers to a supramolecular assembly comprising a cyclic molecule and a copolymer. FIG. 1 depicts a schematic explanatory diagram of polyrotaxane according to the present invention. As shown in FIG. 1, the cyclic molecule is penetrated by a chain of copolymer. In this regard, the term "cyclic molecule" refers to any cyclic molecule that has an internal opening (also referred to as a cavity) large enough for the copolymer to penetrate. In other words, the copolymer penetrates the cyclic molecule by penetrating its opening. However, the cyclic molecule is not covalently attached to the copolymer so that it can rotate around the copolymer forming the axis. In addition, in polyrotaxane, the cyclic molecule is mobile along the copolymer. Such axial mobility occurs within the compartments of the copolymer having a substantially linear structure, which compartments are generally formed from a second polymerizable monomer. In this regard, the term "substantially linear" does not preclude the branching of such compartments (substantially such that the cyclic molecule is rotatable and exhibits mobility along the compartment. As long as a compartment with a linear structure can penetrate the cyclic molecule). In addition, a first polymerizable monomer with a stopper group is incorporated into the copolymer. The structural unit of the copolymer derived from this first monomer having a stopper group prevents cyclic molecules from desorbing from the copolymer. In particular, the stopper group blocks the mobility of the cyclic molecule along the copolymer, thereby preventing the cyclic molecule from decomposing from the copolymer. Therefore, these stopper groups provide stability to the supramolecular structure of polyrotaxane. In this regard, the term "stopper group", as used in the present disclosure, is generally one of the first monomers having a steric bulk sufficient to block the mobility of cyclic molecules along the copolymer. Refers to the department. For example, in order to block the mobility of the cyclic molecule along the copolymer, the stopper group can also be referred to as having a cross section larger than the cross section of the opening of the cyclic molecule. In the methods and polyrotaxanes described herein for preparing polyrotaxane, the first monomer having a stopper group is at least partially incorporated between the ends of the copolymer. This means that the copolymer chain presents a stopper group inside the chain located between the ends of the chain. In the polyrotaxane disclosed herein, the stopper groups need not be located at both ends of the copolymer. However, in addition to the stopper groups between the ends, it does not preclude that the stopper groups are located at one or more ends of the copolymer. In this regard, the term "copolymer end" or "end thereof" refers to the terminal position of the copolymer chain. By setting the upper limit of the first molecule having a stopper group to 20 mol% based on the total amount of the polymerizable monomer of 100 mol%, the length is sufficient to allow the mobility of the cyclic molecule along the copolymer. A compartment containing structural units derived from a second monomer having is provided.

The term "at least", when used in the context of the methods of preparing polyrotaxane described herein and the first and second monomers for polyrotaxane, is used in the context of two or more first monomers having a stopper group. It should be understood that and / or two or more second monomers can be employed. In other words, one, two, three or even more different first monomers with stopper groups may be used. Similarly, 1, 2, 3 or even more different second monomers may be employed. However, in some embodiments, only one first monomer and one second monomer are used. When two or more first monomers are used, the upper limit of 20 mol% based on the total amount of polymerizable monomers of 100 mol% refers to the combined amount of the first monomers.

The term "monomer" or "polymerizable monomer", as used herein throughout the specification, can provide a polymer with many structural units, generally referred to as repeating units, by undergoing polymerization. Represents an active molecule. Thus, the term "polymer" as used herein generally refers to a polymer containing many repeating small units derived from one or more monomers. As a mere example, a monomer is a molecule having one carbon-carbon double bond or a molecule having at least two functional groups per molecule. In particular, the monomer may be a molecule having a low molecular weight.

For the method of preparing the polyrotaxane described herein, the second polymerizable monomer is complexed with a cyclic molecule. Such complexation is typically achieved by inclusion of a second polymerizable monomer in the opening of the cyclic molecule. The second polymerizable monomer complexed by the cyclic molecule is then copolymerized with the first monomer. In this regard, complexation of the first monomer with a stopper group with a cyclic molecule is not always necessary in the method of the invention. However, the complexation of the first monomer is also not excluded. By the method of the present invention, polyrotaxane in which cyclic molecules are penetrated by a copolymer is directly formed. This allows the formation of copolymers and polyrotaxans by performing the methods of the present disclosure, as opposed to the methods of preparing known polyrotaxanes from prior art in which cyclic molecules are passed over pre-prepared polymer chains. Since it is performed in one step, it means that a separate penetration step is not required.

Further, a method for preparing a polyrotaxane known from prior arts such as US 7 943 718 B2, in which a cyclic molecule is passed over a pre-prepared polymer chain, is such that the inclusion complex formed after penetration of the cyclic molecule Isolation and subsequent further steps require that both ends of the polymer chain be capped with bulky blocking groups that prevent cyclic molecules from detaching from the polymer chain. On the other hand, by adopting the method of preparing the polyrotaxane described herein, a first monomer having a stopper group that prevents the cyclic molecule from decomposing is incorporated into the copolymer during the copolymerization. Therefore, as an additional advantage, when carrying out the method of preparing polyrotaxane as described herein, a separate group is attached to the polymer chain to prevent cyclic molecules from desorbing from the polymer after polymerization. You may omit the step of. As a result, the method can save additional steps.

Analytical methods for demonstrating the presence of polyrotaxane structures are known to those of skill in the art. For example, the structure of soluble polyrotaxane can be described in (a) Nuclear Overhauser NMR Spectroscopy (NOESY) (eg, A. Harada, J. Li, MJ Kamachi, J. Am. Chem. Soc. 1994, 116, 3192-3196). (See), (b) diffusion ordered NMR spectroscopy (DOSY), (see, eg, TJ Zhao, HW Beckham, Macromolecules 2003, 36, 9859-9865), and (c) ¹ 1 H NMR spectroscopy (the spread of the signal of a cyclic molecule such as cyclodextrin indicates a penetrated state) (eg, C. Teuchert, C. Michel, F. Hausen, D.-Y. Park, HW Beckham , G. Wenz, Macromolecules 2013, 46, 2-7, see supplementary information). From crystalline samples, using X-ray scattering (see, eg, A. Harada, J. Li, M. Kamachi, Y. Kitagawa, Y. Katsube, Carbohydr. Res. 1998, 305, 127-129). A polyrotaxane structure can be obtained.

It should be noted that the polymerization of monomers complexed with cyclodextrin is disclosed in the prior art (see, eg, WO 01/38408 A2 and WO 97/09354 A1). However, although these documents describe the recovery of cyclodextrin after polymerization, they make no mention of polyrotaxane.

The copolymerization of the methods for preparing polyrotaxanes described herein can be carried out as random copolymerization or block copolymerization.

Therefore, in one embodiment of the method of preparing polyrotaxanes of the present invention, random copolymers are formed (see, eg, exemplary polyrotaxanes shown in FIG. 1a). This method is as follows:
(A) A step of providing a composition containing a cyclic molecule and a first polymerizable monomer having a stopper group;
(B) A step of combining the second polymerizable monomer with the composition of the step (a) and a step of forming a complex of the cyclic molecule and the second monomer; and (c) the composition of the step (b). Including the step of performing radical copolymerization with respect to form a polyrotaxane;
During the copolymerization, a random copolymer penetrating the cyclic molecule is formed, and during the copolymerization, the first monomer having a stopper group is randomly incorporated along the chain of the copolymer.

According to this method, the first and second monomers are combined in step (b). Therefore, the first and second monomers are present simultaneously in the reaction mixture during the copolymerization of step (c). As a result, this method results in the formation of a random copolymer in which the stopper groups are randomly distributed along the copolymer located between the ends of the chain. The random copolymerization of this embodiment may be carried out, as a non-limiting example, as free radical polymerization, atom transfer radical polymerization (ATRP), or reversible addition cleavage chain transfer radical polymerization (RAFT polymerization).

In another embodiment of the method of preparing the polyrotaxane of the present invention, a block copolymer is formed. For example, a method of preparing a polyrotaxane from which a block copolymer is formed (see, eg, the exemplary polyrotaxane shown in FIG. 1b) is described below:
(A) A step of providing a composition containing a cyclic molecule and the second polymerizable monomer;
(B) In the step of performing radical polymerization on the composition of step (a) using a bifunctional radical initiator to form block B containing a repeating unit derived from the second monomer. A step in which the second monomer is complexed with a cyclic molecule;
(C) A step of combining the first polymerizable monomer having a stopper group with the block B; and (d) radical copolymerizing the first polymerizable monomer on both ends of the block B to derive from the first monomer. The step of forming the block A at both ends of the block B including the repeating unit to be formed may be included.
During the copolymerization, an ABA block copolymer is formed, the cyclic molecule is passed over block B, and block B is placed between the first block A and the block A.

In step (b) of the method described in the preceding paragraph, a block, represented as block B, is formed from the second monomer for the purposes of the present disclosure. Since a bifunctional radical initiator is used in step (b), block B presents radical moieties to which radically polymerizable monomers can be further added to both ends of the polymer chain. Therefore, when the first monomer having a stopper group is added to the block B, in the step (d), the first monomer is applied to both ends of the second block when the bifunctional radical initiator is used. Be added. Therefore, by polymerizing the first polymer on both ends of the block B, the block A is formed from the first monomer that leads to the block copolymer having the block sequence ABA, where the block A has a stopper group. It is formed from one monomer and block B is formed from a second monomer. Since the second monomer is complexed by the cyclic molecule, the cyclic molecule is passed over block B. Block A, which is formed from the first monomer having a stopper group, prevents cyclic molecules from decomposing from block B. Preferably, the polymerization steps (b), (c) and (d) are carried out in a one-pot procedure. More preferably, the entire block copolymerization is carried out as a one-pot procedure. This means that the intermediate product is not isolated from the reaction mixture. Alternatively, the polymerization steps may be carried out in reverse order. The bifunctional radical initiator used in this method is not particularly limited. Each initiator having two radical-initiable moieties may be used. For example, 2,5-dimethyl-2,5-bis (benzoylperoxy) hexane; 2,5-dimethyl-2,5-bis (2-ethylhexanoylperoxy) hexane tert-butyl 7-methyl-7- (tert) -Butylazo) Peroxyoctanoate and dibromotoluene / CuBr / N, N, N', N'', N''-pentamethyldiethylenetriamine (PMDETA) are suitable bifunctional radical initiators. The method disclosed herein using a bifunctional radical initiator for block copolymerization may be carried out, for example, as free radical polymerization or as controlled radical polymerization. For example, when a bifunctional radical initiator is used, atom transfer radical polymerization (ATRP) or reversible addition cleavage chain transfer radical polymerization (RAFT polymerization) may be adopted as the controlled radical polymerization technique. For example, the use of controlled radical polymerization such as ATRP or RAFT is particularly preferred with respect to the formation of block copolymers.

In another embodiment of the method of preparing the polyrotaxane of the present invention (see, eg, exemplary polyrotaxane shown in FIG. 1b), the method is described below:
(A) A step of providing a composition containing a first polymerizable monomer having a stopper group;
(B) A step of radically polymerizing the composition of step (a) in the presence of a bifunctional chain transfer agent to form block A containing a repeating unit derived from the first monomer;
(C) The step of combining the second polymerizable monomer with the block A; and (d) the second polymerizable monomer is radically copolymerized with the block A and inserted into the block A and derived from the second monomer. A step of forming a block B containing a repeating unit, comprising a step of copolymerizing the second monomer with a cyclic molecule;
During the copolymerization, an ABA block copolymer is formed, the cyclic molecule is passed over block B, and block B is placed between both blocks A.

In step (b) of the method described in the preceding paragraph, the block represented by block A for the purposes of the present disclosure is formed from a first monomer having a stopper group. Since a bifunctional chain transfer agent is used, a second monomer is inserted into block A in step (d). Finally, repeated insertion of the second monomer forms block B during step (d) containing repeating units inserted into block A and derived from the second polymerizable monomer. Therefore, a block copolymer having the block sequence ABA is obtained in which the block A is formed from the first monomer having a stopper group and the block B is formed from the second monomer. Since the second monomer is complexed by the cyclic molecule, the cyclic molecule is passed over block B. Block A, which is formed from the first monomer having a stopper group, prevents cyclic molecules from decomposing from block B. Preferably, the polymerization steps (b), (c) and (d) are carried out in a one-pot procedure. More preferably, the entire block copolymerization is carried out as a one-pot procedure. This means that the intermediate product is not isolated from the reaction mixture. Alternatively, the polymerization steps may be carried out in reverse order. The bifunctional chain transfer agent used in this method is not particularly limited. Each chain transfer agent having two chains transferable portions may be used. For example, bis (2-propionic acid) trithiocarbonate, S, S'-bis (2-hydroxylethyl-2'-butyrate) trithiocarbonate or S, S'-bis (α, α'-dimethyl- α, α''-acetic acid) -trithiocarbonate is a suitable bifunctional chain transfer agent. The method disclosed herein using a bifunctional chain transfer agent for block copolymerization may be carried out as a reversible additional cleavage chain transfer radical polymerization (RAFT polymerization) as a preferred example.

In the methods described herein, the first monomer having a stopper group is generally used in an amount of 0.1 mol% to 20 mol% based on a total amount of 100 mol% of the polymerizable monomers. Thus, in the polyrotaxans described herein, including cyclic molecules and copolymers that penetrate cyclic molecules, the amount of structural units derived from the first monomer having a stopper group is generally the total amount of structural units of the copolymer. The amount is 0.1 mol% to 20 mol% based on 100 mol%. If the amount of monomers having stopper groups incorporated into the copolymer penetrating the cyclic molecule is greater than 20 mol% based on the total amount of polymerizable monomers of 100 mol%, the amount of bulky stopper groups incorporated into the copolymer will further increase, but On the other hand, the amount of second monomer incorporated into the copolymer is reduced. The second monomer forms a compartment of the copolymer with a substantially linear structure. Cyclic molecules are passed over these substantially linear compartments. These penetrating cyclic molecules are rotatable and mobile along such compartments with a substantially linear structure. When the amount of the first monomer having a stopper group exceeds 20 mol% based on the total amount of the polymerizable monomer of 100 mol%, the amount of the second monomer incorporated into the copolymer is further reduced. Therefore, the length of the compartments of the copolymer having a substantially linear structure formed by the second monomer is reduced. As a result, the free-moving space of the cyclic molecule is reduced. Therefore, the mobility of cyclic molecules along the copolymer chain is limited. Such restrictions on the mobility of cyclic molecules along the copolymer chains make mobile and ring gels useful as self-healing materials, surface coatings, adhesives and paints as described herein. Decreases the ability of the polyrotaxane to form. In contrast, polyrotaxans that are important uses of the polyrotaxans described herein and are capable of forming gels and ring gels useful as self-healing materials, surface coatings, adhesives and paints are described herein. It is obtained when the amount of the first monomer having a stopper group does not exceed 20 mol% based on the total amount of the polymerizable monomer of 100 mol% in the method disclosed in the document. Therefore, in the polyrotaxane described herein, it is preferable that the amount of structural units derived from the first monomer having a stopper group does not exceed 20 mol% based on the total amount of 100 mol% of the structural units of the copolymer. On the other hand, it is easily understood that the amount of stopper groups in the copolymer may be minimal in order to prevent the cyclic compound from decomposing from the copolymer. Therefore, in the method described herein, the amount of monomer having a stopper group is generally at least 0.1 mol% based on 100 mol% of the total amount of polymerizable monomers. Similarly, in the polyrotaxans described herein, the amount of structural units derived from a monomer having a stopper group is generally at least 0.1 mol% relative to a total of 100 mol% of the total structural units of the copolymer.

In some embodiments of the method of preparing the polyrotaxane of the present invention, the amount of the first monomer having a stopper group, particularly in relation to the method of forming a random copolymer or block copolymer, is the amount of the polymerizable monomer. The amount is 0.5 mol% to 18 mol% based on the total amount of 100 mol%. Preferably, the amount of the first monomer having a stopper group is 1 mol% to 16 mol% based on 100 mol% of the total amount of the polymerizable monomers. More preferably, the amount of the first monomer having a stopper group is 2 mol% to 15 mol% based on 100 mol% of the total amount of the polymerizable monomers. Even more preferably, the amount of the first monomer having a stopper group is 3 mol% to 12 mol% based on 100 mol% of the total amount of the polymerizable monomers. Most preferably, the amount of the first monomer is 5 mol% to 11 mol% based on 100 mol% of the total amount of the polymerizable monomer.

Also described herein is another embodiment of the method of preparing a polyrotaxane in which a block copolymer is formed. This method is as follows:
(A) A step of providing a composition containing a first polymerizable monomer having a stopper group;
(B) A step of performing radical polymerization on the composition of step (a) to form a block A containing a repeating unit derived from the first monomer having a stopper group;
(C) A step of radically copolymerizing the second polymerizable monomer with the block A to form a block B containing a repeating unit derived from the second polymerizable monomer attached to the block A. The second monomer is complexed with the cyclic molecule; and (d) the third polymerizable monomer having a stopper group is radically copolymerized with the block B to form the block C. Includes steps in which the third monomer is the same as or different from the first monomer;
During the copolymerization, an ABC block copolymer is formed, the cyclic molecule is passed over block B, and block B is placed between block A and block C; and said first having a stopper group. The amount of the combination of one monomer and the third monomer is 0.1 mol% to 20 mol% based on the total amount of the polymerizable monomer of 100 mol%.

According to the step (b) of the method described in the previous section, the first monomer having a stopper group is polymerized to form a block A. Then, in step (c), the second monomer is polymerized on the end of block A to form block B. Finally, in step (d), a third monomer having a stopper group is polymerized on the end of block B. Therefore, by polymerizing the second polymer on the ends of block A and then the third polymer on the ends of block B, blocks A and C are formed from monomers having stopper groups, and , A block copolymer having the block sequence ABC, in which the block B is formed from the second monomer, is formed. Since the second monomer is complexed by the cyclic molecule, the cyclic molecule is passed over block B. With respect to the first monomer having a stopper group and the second monomer having a stopper group, the first monomer and the second monomer may be the same or different. If the first monomer and the third monomer are the same, block C may also be represented as block A. Preferably, the polymerization steps (b), (c) and (d) are carried out in a one-pot procedure. More preferably, the entire block copolymerization is carried out as a one-pot procedure. This means that the intermediate product is not isolated from the reaction mixture. The block copolymerization of this embodiment may be carried out as, as a non-limiting example, as free radical polymerization, atom transfer radical polymerization (ATRP), or reversible addition cleavage chain transfer radical polymerization (RAFT polymerization).

Further, when the ABC block copolymer is formed, the combination amount of the first monomer and the third monomer having a stopper group is generally 100 mol% of the total amount of the polymerizable monomer for the reason shown in the present specification. The standard is in the range of 0.1 mol% to 20 mol%. In particular, the amount of combination of the first monomer and the third monomer having a stopper group is a mobile gel useful as a self-healing material, a surface coating agent, an adhesive and a paint as described and described herein. In order to provide a polyrotaxane capable of forming a ring gel, it generally does not exceed 20 mol% based on a total amount of 100 mol% of polymerizable monomers.

The method by which the polyrotaxane containing the block A, the block B and the copolymer having the block C is formed, and the block C polymerizes the second monomer into the block A and the third monomer into the block B. In certain embodiments of the method formed by the above, the combined amount of the first monomer having a stopper group and the third monomer is 0.5 mol% to 18 mol% based on 100 mol% of the total amount of the polymerizable monomer. Is the amount of. Preferably, the amount of the combination of the first monomer and the third monomer having a stopper group is 1 mol% to 16 mol% based on 100 mol% of the total amount of the polymerizable monomers. More preferably, the amount of the combination of the first monomer and the third monomer having a stopper group is 2 mol% to 15 mol% based on 100 mol% of the total amount of the polymerizable monomers. Even more preferably, the amount of the combination of the first monomer and the third monomer having a stopper group is 3 mol% to 12 mol% based on the total amount of the polymerizable monomer of 100 mol%. Most preferably, the amount of the combination of the first monomer and the third monomer having a stopper group is 5 mol% to 11 mol% based on 100 mol% of the total amount of the polymerizable monomers. Further, in these embodiments, the first monomer having a stopper group and the third monomer having a stopper group may be the same or different.

Preferably, in some embodiment of any one of the methods of preparing polyrotaxanes described herein, cyclic molecules are passed over the backbone of the copolymer. This means that the main chain polyrotaxane is formed in a preferred embodiment of the method.

Preferably, in embodiments of the methods of preparing polyrotaxanes described herein, radical polymerization or copolymerization is carried out using radical initiators. In some embodiments, the radical initiator is included in the composition provided in step (a). In particular, the term "initiator" or "radical initiator", as used herein, refers to an active molecule capable of initiating polymerization. In general, in polymerization, the initiator may be used in a small amount compared to the amount of the monomer (s). The initiator may provide a building block for the polymer.

In some embodiments of the methods described herein, the composition provided in step (a) is deoxidized before being subjected to polymerization. Oxygen scavenging removes oxygen from the composition at least partially, preferably substantially completely. This is because otherwise oxygen can promote the oxidation of radical species during the copolymerization and thus act as an inhibitor.

In some embodiments of the method of preparing polyrotaxane, the polymerization is initiated thermally and / or photochemically, especially when radical polymerization is carried out using a radical initiator. In one embodiment, the polymerization is thermally initiated. In another embodiment, the polymerization is photochemically initiated. In yet another embodiment, the polymerization is initiated thermally and photochemically. In this regard, the radical initiators used for thermal and / or photochemical initiation are not particularly limited, and those skilled in the art are suitable for any radical initiator and / or thermal initiation suitable for thermal initiation. Any radical initiator may be appropriately selected and used. Suitable radical initiators are selected from, for example, the group consisting of persulfates, hydrogen peroxide, organic peroxides, azo initiators, and any combination thereof.

In some embodiments, the polymerization is accelerated by adding an initiator for radical initiation. Accelerators for radical initiation that can be suitably used in the context of the present invention include, for example, thiosulfate, metasulfite, N, N, N', N'-tetramethylethylenediamine or a salt thereof, ethylenediaminetetra. It is selected from the group consisting of acetic acid or a salt thereof, a peroxidase enzyme, and any combination thereof.

The various cyclic molecules used in the polyrotaxane may be employed in the methods of preparing the polyrotaxanes disclosed herein. For example, the cyclic molecule may be a crown ether, cucurbituril [n] uryl, calixarene, cyclic amide and / or transition metal complex. However, in some particularly preferred embodiments of the methods of the invention, the cyclic molecule is selected from the group consisting of cyclodextrins, cyclodextrin derivatives and any combination thereof. In one embodiment, the cyclic molecule is cyclodextrin. In another embodiment, the cyclic molecule is a cyclodextrin derivative. In some embodiments of the method, cyclodextrin and cyclodextrin derivatives are used in combination. As is known to those skilled in the art, the term "cyclodextrin" refers to a cyclic oligosaccharide compound. As a non-limiting example, such cyclic oligosaccharide compounds include 6 sugar units (α-cyclodextrin), 7 sugar units (β-cyclodextrin), or 8 sugar units (γ-cyclodextrin). It's fine.

In some embodiments, the cyclodextrin or cyclodextrin derivative is a natural cyclodextrin, methylated cyclodextrin, acetylated cyclodextrin, hydroxyethylated cyclodextrin, hydroxypropylated cyclodextrin, cationic cyclodextrin derivative, yin. It is selected from the group consisting of ionic cyclodextrin derivatives, glucosylated cyclodextrins, chemically reactive cyclodextrin derivatives, and any combination thereof. In some embodiments, the cyclodextrin or cyclodextrin derivative is α-cyclodextrin, randomly methylated α-cyclodextrin, β-cyclodextrin, randomly methylated β-cyclodextrin (RAMEB), Hydroxypropyl β-cyclodextrin, acetyl β-cyclodextrin, heptaxis (2,6-di-O-methyl) -β-cyclodextrin, carboxymethyl-β-cyclodextrin, succinyl-β-cyclodextrin, (2-carboxy) Ethyl) -β-cyclodextrin, β-cyclodextrin, sulfobutylated β-cyclodextrin, β-cyclodextrin sulfate, 6-monodeoxy-6 monoamino-β-cyclodextrin hydrochloride, heptaxis-6-deoxy-6- Amino) -β-cyclodextrin, (2-hydroxy-3-N, N, N-trimethylamino) propyl-β-cyclodextrin, heptaxis (2,6-tri-O-methyl) -β-cyclodextrin, mono -Amino-β-cyclodextrin, sulfobutyl-β-cyclodextrin, γ-cyclodextrin, randomly methylated γ-cyclodextrin, 2-hydroxy-3-N, N, N-trimethylaminopropyl-β-cyclo It is selected from the group consisting of dextrin halides, salts thereof, and any combination thereof. In some embodiments, the cyclodextrin or cyclodextrin derivative is a sodium carboxymethyl-α-cyclodextrin salt, a sodium carboxymethyl-β-cyclodextrin salt, succinyl-α-cyclodextrin, succinyl-β-cyclodextrin, Succinyl-γ-cyclodextrin, (2-carboxyethyl) -α-cyclodextrin, (2-carboxyethyl) -β-cyclodextrin, α-cyclodextrin sodium salt, β-cyclodextrin sodium salt, γ -Sodium cyclodextrin phosphate, sulfobutylated β-cyclodextrin sodium salt, sulfobutylated β-cyclodextrin sodium salt, sulfobutylated β-cyclodextrin sodium salt, α-cyclodextrin sodium sulfate salt, β-cyclodextrin sodium sulfate salt , Γ-Cyclodextrin sodium sulfate, 6-monodeoxy-6-monoamino-β-cyclodextrin hydrochloride, heptaxi (6-deoxy-6-amino) -β-cyclodextrin heptahydrochloride, octakis (6-deoxy-) Selected from the group consisting of 6-amino) -γ-cyclodextrin octahydrochloride, (2-hydroxy-3-N, N, N-trimethylamino) propyl-β-cyclodextrin chloride, and any combination thereof. It is an ionic cyclodextrin or an ionic cyclodextrin derivative.

In certain preferred embodiments, the cyclodextrin derivative is a randomly methylated β-cyclodextrin (RAMEB). RAMEB, also known as methyl-β-cyclodextrin (CAS Number 128446-36-6), is produced from β-cyclodextrin on an industrial scale. The methyl substituents are randomly distributed between the hydroxyl groups at the 2, 3 and 6 positions of each of the anhydrous glucose units. The average degree of substitution (DS) per unit of anhydrous glucose is producer-dependent and ranges from 1.3 to 2.3, preferably between 1.6 and 2.0. As one advantage, the solubility of RAMEB and its clathrate compounds in water exceeds that of natural β-cyclodextrin. Β-Cyclodextrin in which all hydroxyl groups are not substituted may also be referred to as “natural β-cyclodextrin”.

As long as the first monomer has a stopper group that is sterically bulky enough to block the mobility of the cyclic molecule along the copolymer and to prevent the cyclic molecule from decomposing from the copolymer chain. , The first monomer is not particularly limited. Preferably, the first monomer having a stopper group is a vinyl monomer. The term "vinyl monomer", as used throughout this specification, generally refers to a monomer having a vinyl group. In this regard, the term "vinyl group" refers to the group-CH = CH ₂ . Optionally, the vinyl group can carry one or more substituents instead of any one of the hydrogen atoms (eg, methyl group in poly (ethylene glycol) methacrylate). Preferably, the first monomer has a molecular weight of 70 g / mol or more. Therefore, in some embodiments of the method of preparing polyrotaxane, the first monomer having a stopper group may have a molecular weight of 70 g / mol to 1000 g / mol, preferably 100 g / mol to 500 g / mol.

In some embodiments, the first monomer is myrsen, an aromatic vinyl monomer, N-isopropyl (meth) acrylamide, N-vinylcaprolactam, N-vinylimidazole, poly (ethylene glycol) (meth) acrylate, α. , Ω-Bis (meth) acrylate, and any combination thereof. When the first monomer is poly (ethylene glycol) (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is preferably 3000 g / mol or less. More preferably, when the first monomer is poly (ethylene glycol) (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is 1000 g / mol or less. In certain embodiments, the first monomer is poly (ethylene glycol) methyl ether (meth) acrylate. In certain embodiments, the first monomer is hydroxyethyl (meth) acrylate. In some embodiments where the first monomer having a stopper group is an aromatic vinyl monomer, the aromatic vinyl monomer is optionally substituted styrene, optionally substituted styrene sulfonic acid, optionally substituted. It is selected from the group consisting of vinylpyridines, optionally substituted divinylbenzenes, and any combination thereof. The term "sometimes substituted" is mentioned in the context of occasionally substituted styrene, sometimes substituted styrene sulfonic acid, sometimes substituted vinylpyridine and sometimes substituted divinylbenzene. If so, it is independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 haloalkyl, C1-C10 alkoxy, CN, nitro, halogen (F, Cl, Br, I) and the like. Represents one or more substituents to be made. For example, in one embodiment, the aromatic vinyl monomer is 4- (trifluoromethyl) styrene. When α, ω-bis (meth) acrylate is used, in embodiments, the α, ω-bis (meth) acrylate is ethylene glycol, oligoethylene glycol, poly (ethylene glycol), bisphenol A and any of them. Α, ω-bis (meth) glycolate of the mixture of. When the α, ω-bis (meth) acrylate is a poly (ethylene glycol) α, ω-bis (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is preferably 3000 g / mol or less. More preferably, when the α, ω-bis (meth) acrylate is a poly (ethylene glycol) α, ω-bis (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is 1000 g / mol or less. The term "(meta) acrylate" covers both acrylate and methacryllate when used in any context throughout this disclosure.

Further, the second monomer is not particularly limited as long as the second monomer can form a compartment of the copolymer having a substantially linear structure. Therefore, the second monomer may be a substantially linear monomer. As mentioned above, the term "substantially linear" does not preclude the branching of such compartments (so that the cyclic molecule is rotatable and exhibits mobility along the compartment). As long as a compartment with a linear structure can penetrate the cyclic molecule). As a result, the second monomer may be branched, preferably slightly branched, as long as the branch does not prevent the rotation of the cyclic molecule and the mobility of the cyclic molecule along the copolymer. Preferably, the second monomer is a vinyl monomer. More preferably, both the first monomer and the second monomer having a stopper group are vinyl monomers. Preferably, in any one of the methods disclosed herein, the second monomer has a molecular weight of 120 g / mol or less, more preferably 110 g / mol or less.

In any one of the methods described herein, the second monomer may be a nonionic monomer. Preferably, the term "nonionic monomer", as used herein, has no charged functionality when in aqueous solution having a pH range of 2-11, more preferably 3-10. Represents a monomer. The term "nonionic monomer" as used herein includes, for example, monomers having only structural units and / or functional groups that are non-ionizable, such as isoprene or methylmethacrylate. In addition, the term nonionic monomer is also generally capable of forming ions, such as carboxylic acid groups, but is in an uncharged state when in aqueous solution with a pH range of 2-11, more preferably 3-10. May include monomers having the functional groups in. Examples of such nonionic monomers that are uncharged within such a pH range are acrylic acids having a carboxylic acid group and derivatives thereof, such as methacrylic acid.

Preferably, in some embodiments of the methods of preparing polyrotaxanes disclosed herein, the second monomer is a hydrophobic monomer. In particular, the second monomer is a nonionic hydrophobic monomer. As used herein in the context of any one of the methods of preparing polyrotaxane and any polyrotaxane, the term "hydrophobic monomer" refers to a monomer that is insoluble in water or sparingly soluble in water. For the methods of preparing polyrotaxanes described herein and for the purposes of polyrotaxans, the hydrophobic monomers are preferably less than 20 g / l, more preferably less than 10 g / l, even more preferably in water at 20 ° C. Has a solubility of less than 5 g / l, and most preferably less than 2 g / l. When a cyclodextrin or a cyclodextrin derivative is used as a cyclic molecule, a nonionic monomer, particularly a hydrophobic monomer, is preferred. It has been difficult to obtain polyrotaxane through cyclodextrin on a hydrophobic polymer chain such as polyisoprene or polybutadiene chain. By applying the methods disclosed herein, where the second monomer is complexed with cyclodextrin and then copolymerized, a polyrotaxane comprising a hydrophobic copolymer chain, such as a polyisoprene-or polybutadiene-containing copolymer chain. Is easily obtained. In some embodiments, the second monomer is selected from the group of vinyl monomers having a molecular weight of less than 120 g / mol. Preferably, the second monomer is selected from the group of vinyl monomers having a molecular weight less than 110 g / mol. Additional or alternative, the second monomer is 1,3-diene, 1,3,5-triene, (meth) acrylate, vinyl ester, vinyl-ether, (meth) acrylonitrile, (meth) acrylic acid. , (Meta) acrylamide, and any combination thereof may be selected from the group of vinyl monomers. When the second monomer is 1,3-diene, the 1,3-diene is preferably selected from 1,3-butadiene, derivatives of 1,3-butadiene, isoprene, and any combination thereof. To. Therefore, in one embodiment, 1,3-butadiene is used. In one embodiment, isoprene is used. In another embodiment, 1,3-butadiene and isoprene are used in combination. In one embodiment, 1,3-diene is dimethyl butadiene. When the second monomer is a vinyl ester, in some embodiments the vinyl ester is vinyl acetate. When the second monomer is a vinyl ether, in some embodiments, the vinyl ether is a methyl-vinyl ether. When the second monomer is (meth) acrylate, the (meth) acrylate is selected from the group consisting of methylacryllate, methylmethacrylate and any combination thereof. Therefore, in one embodiment, the second monomer is methylacryllate. In one embodiment, the second monomer is methylmethacrylate. In another embodiment, methylacryllate and methylmethacrylate are used in combination. The term "(meth) acrylonitrile" covers both acrylonitrile and methacrylonitrile as used in any context throughout the present disclosure. The term "(meth) acrylic acid" covers both acrylic acid and methacrylic acid as used in any context throughout the present disclosure. The term "(meth) acrylamide" covers both acrylamide and methacrylamide as used in any context throughout this disclosure.

In one preferred embodiment of any one of the methods of preparing polyrotaxane disclosed herein, the first monomer having a stopper group is a poly (ethylene glycol) methyl ether methacrylate and the second monomer is , Isoprene, and the cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). In addition, in this embodiment, randomly methylated β-cyclodextrin (RAMEB) and 2-hydroxy-3-N, N, N-trimethylamino) propyl-β-cyclodextrin chloride (cationic cyclic molecule). May be used in combination. These combinations of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

In another preferred embodiment of any one of the methods of preparing polyrotaxans described herein, the first monomer having a stopper group is styrene, the second monomer is isoprene, and The cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

In another preferred embodiment of any one of the methods for preparing polyrotaxans disclosed herein, the first monomer having a stopper group is myrcene, the second monomer is isoprene, and The cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers or block copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

In another preferred embodiment of any one of the methods of preparing a polyrotaxane as described herein, the first monomer having a stopper group is a poly (ethylene glycol) monomethacrylate (PEGMA). The second monomer is isoprene and the cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

In another preferred embodiment of any one of the methods of preparing a polyrotaxane as described herein, the first monomer having a stopper group is styrene and the second monomer is methylacryllate. Yes, and the cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

In another preferred embodiment of any one of the methods of preparing a polyrotaxane as described herein, the first monomer having a stopper group is a poly (ethylene glycol) methyl ether methacrylate, the second. The monomer of is dimethyl butadiene, and the cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

In another preferred embodiment of any one of the methods of preparing polyrotaxans as described herein, the first monomer having a stopper group is hydroxyethyl methacrylate and the second monomer is isoprene. And the cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is β-cyclodextrin. This combination of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

In another preferred embodiment of any one of the methods of preparing polyrotaxane as described herein, the first monomer having a stopper group is poly (ethylene glycol) methyl ether methacrylate, the second. The monomer of is isoprene, and the cyclic molecule is hydroxypropylated cyclodextrin. Preferably, in this embodiment, the cyclic molecule is hydroxypropyl-β-cyclodextrin. This combination of monomers and cyclic molecules may be used in any of the methods described herein leading to the formation of random copolymers. Preferably, when such monomers are used, radical copolymerization is carried out in an aqueous medium, more preferably in water.

According to a preferred embodiment of the method of preparing polyrotaxane disclosed herein, the copolymerization is carried out in an aqueous medium. For example, the aqueous medium is an aqueous solution or suspension. Preferably, the copolymerization is carried out in water. In particular, when the cyclic molecule is selected from the group consisting of cyclodextrins, cyclodextrin derivatives and any combination thereof, the copolymerization is preferably carried out in an aqueous medium. We do not want to be bound by any theory, but water is a cyclodextrin or cyclodextrin derivative and a second, especially if the second monomer is a nonionic monomer, preferably a hydrophobic monomer. It is considered to assist the formation of a complex with the polymerizable monomer of.

In embodiments of the methods described herein for preparing polyrotaxane, the copolymerization is carried out using a water-soluble radical initiator, especially if the copolymerization is carried out in an aqueous medium. In some embodiments, the water-soluble radical initiator is a persulfate, hydrogen peroxide, organic peroxide, hydrophilic azo-initiator, water-soluble complex of the azo initiator and a cyclodextrin or cyclodextrin derivative. , And any combination thereof. In one embodiment, a water-soluble complex of azo initiator and cyclodextrin is used. In one embodiment, a water-soluble complex of azo initiator and cyclodextrin derivative is used. In another embodiment, a water-soluble complex of an azo initiator and a cyclodextrin and a water-soluble complex of an azo initiator and a cyclodextrin derivative are used in combination. In some embodiments, the water-soluble radical initiator is peroxodisulfate, tert-butyl hydroperoxide, 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, azobis. It is selected from the group consisting of -isobutyramidine, 4,4'-bis (dimethylamino) benzophenone, and any combination thereof. The radical initiators that may be used are not limited to the initiators explicitly listed herein, and one of ordinary skill in the art will practice the method of preparing the polyrotaxanes disclosed herein. It will be known how to select a suitable initiator. Suitable initiators are, for ^{example, Polymer Handbook, 4 th edition,} by J. Barndrup, EH Immergut, EA Grulke, John Wiley and Sons, Inc., disclosed in 1999, pp. II / 2- II / 69 .. The initiator combinations disclosed in this reference can also be suitably used.

In addition to using radical initiators, in some embodiments, accelerators for radical initiation are used, especially when water-soluble radical initiators are used. For example, the accelerator for radical initiation includes thiosulfate, metasulfite, N, N, N', N'-tetramethylethylenediamine or a salt thereof, ethylenediaminetetraacetic acid or a salt thereof, peroxidase enzyme, and theirs. Selected from a group consisting of any combination. As is known to those skilled in the art, radical initiators can interact with, for example, radical initiators to form so-called redox initiators. However, other mechanisms of interaction between radical initiators and radical initiators can occur as well. Furthermore, the accelerator for radical initiation is not limited to the above-mentioned specific examples. In this regard, one of ordinary skill in the art may appropriately select and use any accelerator for radical initiation described in, for example, A.S. Sarac, Prog. Polym. Sci. 1999, 24, 1149-1204.

In some embodiments, the copolymerization of any one of the methods for preparing polyrotaxanes described herein is carried out using a chain transfer agent. Chain transfer agents are used, especially when the copolymerization is carried out using RAFT polymerization techniques. In some embodiments, the chain transfer agent is selected from the group consisting of dithioesters, xanthates, dithiocarbamate, trithiocarbanates, derivatives of any one of the chain transfer agents described above, and any combination thereof. To. Such chain transfer agents have the following general structure:

[In the formula, radicals R and R'may be selected independently of alkyl, aryl, etc.]
It is particularly useful when the copolymerization of the method disclosed in the present specification is carried out as RAFT polymerization. As an example, S, S'-bis (α, α'-dimethyl-α''-acetic acid) -trithiocarbonate can be used as a chain transfer agent in the methods described herein. As is known to those skilled in the art, the chain transfer agent should preferably be water soluble when the copolymerization is carried out in an aqueous medium. When a cyclodextrin or cyclodextrin derivative is used as a cyclic molecule, good results can also be achieved if the chain transfer agent is solubilized by the cyclodextrin or cyclodextrin derivative. Without wishing to be bound by any theory, solubilization of chain transfer agents may be achieved by forming a complex of the chain transfer agent with a cyclodextrin or cyclodextrin derivative. The chain transfer agents that can be used in the methods described herein are not limited to the specific examples described above. Other chain transfer agents, such as those described in C. Barner-Kowollik, Handbook of RAFT Polymerization, Wiley-VCH, 2008, pp. 1-543, may be used.

The technique for carrying out radical copolymerization of any one of the methods for preparing the polyrotaxane of the present disclosure is not particularly limited. For example, in some embodiments, radical copolymerization may be carried out using any free radical polymerization technique known to those of skill in the art.

In some embodiments, controlled radical polymerization techniques may be employed. In this regard, in some embodiments, the copolymerization is carried out using reversible add-cracking chain transfer polymerization (RAFT polymerization). RAFT polymerization applies chain transfer agents to control molecular weight and polydispersity. After initiation, the chain transfer agent can reversibly stop the extending chain, and a fragment of the chain transfer agent initiates a new chain. RAFT polymerization techniques that provide the same polymerizable properties as living polymerization can reduce the free radical concentration at any given time point. Suitable RAFT polymerization techniques are generally known to those of skill in the art and can be found, for example, in the Handbook of RAFT Polymerization, C. Barner-Kowollik (Ed.), Wiley-VCH, Weinheim, 2008.

In other embodiments, the copolymerization is carried out using atom transfer radical polymerization (ATRP). ATRP also corresponds to living polymerization technology. ATRPs also use organic halides as initiators and metal ligand complexes as catalysts when applied in the methods of preparing polyrotaxans described herein. The transfer of halogen atoms between the initiator, the growing chain and the catalyst provides a low concentration of radicals at a given time point. ATRP techniques are known to those of skill in the art and are appropriately selected. For example, suitable ATRP techniques are described in K. Matyjaszewski, JH Xia, Chem. Rev. 2001, 101, 2921-2990. In some embodiments, the initiator-catalyst combination for atom transfer radical polymerization was solubilized with a water-soluble initiator-catalyst combination, cyclodextrin, especially when the copolymerization is carried out in an aqueous medium. It is selected from the group consisting of a combination of initiator and catalyst, and any combination thereof. In one embodiment, the initiator and catalyst combination for ATRP is a water soluble initiator and catalyst combination. In one embodiment, the initiator and catalyst combination for ATRP is an initiator and catalyst combination solubilized by cyclodextrin. In other embodiments, the water-soluble initiator and catalyst combination is used in combination with the cyclodextrin-solubilized initiator and catalyst combination. For example, the combination of water-soluble initiator and catalyst may be a combination of hydrophilic 2-halogeno-isobutyrate or hydrophilic 2-halogenopropionate, Cu (I) salt and chelating diamine, hydrophilic 2-halogeno-isobutyrate or hydrophilic. It may be selected from the group consisting of a combination of sex 2-halogenopropionate and an oxidoreductase, and any combination thereof. In certain embodiments, the combination of water-soluble initiator and catalyst is a combination of hydrophilic 2-halogeno-isobutyrate, Cu (I) salt and chelating diamine. In certain embodiments, the combination of water-soluble initiator and catalyst is a combination of hydrophilic 2-halogenopropionate, Cu (I) salt and chelating diamine. In certain embodiments, the combination of water-soluble initiator and catalyst is a combination of hydrophilic 2-halogeno-isobutyrate and oxidoreductase. In certain embodiments, the combination of water-soluble initiator and catalyst is a combination of hydrophilic 2-halogenopropionate and oxidoreductase. In other embodiments, combinations of these combinations of water-soluble initiators and catalysts are used. In some embodiments, the hydrophilic 2-halogeno-isobutyrate is hydroxyethyl-2-bromoisobutyrate. In some embodiments, the chelating diamines are ethylenediamine, 2,2'-bipyridine (bpy), 4,4'-di (5-nonyl) -2,2'-bipyridine (dNbpy), N, N, N', N'-tetramethylethylenediamine (TMEDA), N-propyl (2-pyridyl) methaneimine (NPrPMI), 2,2': 6', 2''-terpyridine (tpy), 4,4', 4''-Tris (5-nonyl) -2,2': 6', 2''-terpyridine (tNtpy), N, N, N', N'', N''-pentamethyldiethylenetriamine (PMDETA), N, N-bis (2-pyridylmethyl) octylamine (BPMOA), 1,1,4,7,10,10-hexamethyl-triethylene-tetramine (HMTETA), tris [2- (dimethylamino) ethyl] amine (Me) ₆ TREN), Tris [(2-pyridyl) methyl] amine (TPMA), 1,4,8,11-tetraaza-1,4,8,11-tetramethylcyclotetradecane (Me4CYCLAM), N, N, N' , N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), diethylenetriamine (DETA), triethylenetetramine (TETA), N, N-bis (2-pyridylmethyl) amine (BPMA), tris [2-aminoethyl] ] Amine (TREN), 1,4,8,11-tetraazacyclotetradecane (CYCLAM), N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), N, N, N' , N'', N''-Selected from the group consisting of pentamethyldiethylenetriamine. Any combination of the chelating diamines described above may be used. In some embodiments, the redox enzyme is hemoglobin. The ATRP methods using hemoglobin and suitable for the copolymerization described herein include, for example, TB Silva, M. Spulber, MK Kocik, F. Seidi, H. Charan, M. Rother, SJ Sigg, K. It is described in Renggli, G. Kali, N. Bruns, Biomacromolecules 2013, 14, 2703-2712.

The temperature at which the copolymerization of any one of the methods for preparing the polyrotaxane disclosed in the present specification is carried out is not particularly limited, and those skilled in the art can appropriately select this. For example, the copolymerization may be carried out at a temperature of 80 ° C. or lower. Preferably, the copolymerization is carried out at a temperature of 35 ° C. or lower. It is preferable to carry out the copolymerization at a temperature of 0 ° C. or higher.

In any one of the methods of preparing polyrotaxane described herein, filtration may be used to isolate polyrotaxane. As an example, ultrafiltration may be used. Polyrotaxane may be heated prior to filtration. After filtration, the polyrotaxane may be dried. Preferably, the drying of polyrotaxane is carried out using lyophilization. However, those skilled in the art may appropriately select and apply other suitable drying methods.

The present invention is also a polyrotaxane comprising one cyclic molecule and one copolymer penetrating the cyclic molecule, wherein the copolymer is from one first polymerizable monomer having at least (a) one stopper group. A nonionic copolymer comprising a derived structural unit and at least (b) a structural unit derived from one second polymerizable monomer, wherein the structural unit derived from the first monomer having a stopper group is The structure, which is at least partially incorporated between both ends of the chain of the copolymer, prevents the cyclic compound from decomposing from the copolymer and is derived from the first monomer having a stopper group. With respect to polyrotaxane, the amount of the unit is 0.1 mol% to 20 mol% based on 100 mol% of the total structural units of the copolymer.

The copolymer that penetrates the cyclic molecule of such polyrotaxane of the present invention is a nonionic copolymer, and the first and second monomers are nonionic monomers. Preferably, the term "nonionic monomer" also, when used herein with respect to polyrotaxane, has a charged functionality when in aqueous solution having a pH range of 2-11, more preferably 3-10. Represents a monomer that does not exist. The term "nonionic monomer" as used herein includes, for example, monomers having only structural units and / or functional groups that are non-ionizable, such as isoprene or methylmethacrylate. In addition, the term nonionic monomer is also generally capable of forming ions, such as carboxylic acid groups, but is in an uncharged state when in aqueous solution with a pH range of 2-11, more preferably 3-10. It may include a monomer having a functional group in. Examples of such nonionic monomers that are uncharged within such a pH range are acrylic acids having a carboxylic acid group and derivatives thereof, such as methacrylic acid. Preferably, the term "nonionic copolymer" is a copolymer that has substantially no structural units, including functionalities, that are charged when in aqueous solution with a pH range of 2-11, more preferably 3-10. Point to. The term "nonionic copolymer" as used herein is used, for example, as a structural unit derived from a copolymer having only non-ionizable structural units and / or functional groups, such as isoprene or methylmethacrylate. Including. In addition, the term nonionic copolymer is also generally capable of forming ions, such as carboxylic acid groups, but is in an uncharged state when in aqueous solution with a pH range of 2-11, more preferably 3-10. Copolymers having structural units and / or functional groups in the above may also be included. An example of such a structural unit that is uncharged within such a pH range is a structural unit derived from acrylic acid having a carboxylic acid group and its derivatives, such as methacrylic acid. With respect to nonionic copolymers, "substantially free of structural units containing functional charges when in aqueous solutions in the pH range 2-11, more preferably 3-10" is preferably 2. It means that there are only a small amount of functional units in the copolymer that are charged when they are in an aqueous solution in the pH range of ~ 11, more preferably 3-10. For example, such structural units, including functionalities that are charged when in an aqueous solution in the pH range of 2-11, more preferably 3-10, may come from impurities in the monomer to be copolymerized, or from a copolymerization reaction. It can be derived from the reactants used in, such as initiators, catalysts and / or chain transfer agents, or from ionic monomers intentionally added to the reaction mixture. The amount of functional units, each containing functionality charged when in aqueous solution in the pH range of 2-11, more preferably 3-10, is less than 5 mol%, respectively, relative to 100 mol% of the copolymer's structural units. , More preferably less than 3 mol%, even more preferably less than 2 mol%, most preferably less than 1 mol%.

In a preferred embodiment of the polyrotaxane of the present invention, the polyrotaxane can or is obtained by any one of the methods of the invention described herein.

In one embodiment of the polyrotaxane of the present invention, the copolymer is such that the structural unit derived from the first polymerizable monomer having a stopper group is at least partially between both ends along the chain of the copolymer. It is a random copolymer incorporated at random.

In some embodiments of the polyrotaxane of the present invention, the amount of said structural units derived from the first monomer having a stopper group is 0.5 mol% to 18 mol% based on 100 mol% of the total structural units of the copolymer. The quantity. Preferably, the amount of the structural unit derived from the first monomer having a stopper group is 1 mol% to 16 mol% based on 100 mol% of the total structural unit of the copolymer. More preferably, the amount of the structural unit derived from the first monomer having a stopper group is 2 mol% to 15 mol% based on 100 mol% of the total structural unit of the copolymer. Even more preferably, the amount of the structural unit derived from the first monomer having a stopper group is 3 mol% to 12 mol% based on 100 mol% of the total structural unit of the copolymer. Most preferably, the amount of the structural unit derived from the first monomer is 5 mol% to 11 mol% based on 100 mol% of the total structural unit of the copolymer.

In another embodiment of the polyrotaxane of the present invention, the copolymer comprises a block A comprising a repeating unit derived from the first polymerizable monomer having a stopper group and a repeating derived from the second polymerizable monomer. A block copolymer containing a block B containing a unit and a block C containing a repeating unit derived from a third polymerizable monomer, wherein the repeating unit derived from the third monomer is the first monomer. Same or different from the repeating unit derived from, in the block copolymer, the block B is placed between the block A and the block C, the cyclic molecule is passed over the block B, and the first. The amount of the combination of the structural unit derived from one monomer and the structural unit derived from the third monomer is 0.1 mol% to 20 mol% based on the total amount of 100 mol% of the structural units of the copolymer. , Block copolymer. If the repeating unit derived from the third monomer in block C and the repeating unit derived from the first monomer in block A are the same, block C may also be represented as block A.

In certain embodiments of the polyrotaxane comprising the block A, the block B and the block copolymer having the block C, the structural unit derived from the first monomer having a stopper group and the said derived from the third monomer. The amount of the combination of structural units is 0.5 mol% to 18 mol% based on the total amount of 100 mol% of the structural units of the copolymer. Preferably, the combination amount of the structural unit derived from the first monomer having a stopper group and the structural unit derived from the third monomer is 1 mol% based on the total amount of 100 mol% of the structural units of the copolymer. The amount is ~ 16 mol%. More preferably, the combination amount of the structural unit derived from the first monomer having a stopper group and the structural unit derived from the third monomer is 2 mol based on 100 mol% of the total structural unit of the copolymer. The amount is from% to 15 mol%. Even more preferably, the combination amount of the structural unit derived from the first monomer having a stopper group and the structural unit derived from the third monomer is based on 100 mol% of the total amount of the structural units of the copolymer. The amount is 3 mol% to 12 mol%. Most preferably, the combination amount of the structural unit derived from the first monomer having a stopper group and the structural unit derived from the third monomer is 5 mol% to 5 mol% based on the total amount of 100 mol% of the structural units of the copolymer. The amount is 11 mol%. Further, in these embodiments, the first monomer having a stopper group and the third monomer having a stopper group may be the same or different.

Preferably, in some embodiments of the polyrotaxanes described herein, cyclic molecules are threaded over the backbone of the copolymer. This means that in a preferred embodiment, the polyrotaxane is a backbone polyrotaxane.

Various cyclic molecules commonly used in polyrotaxanes may be employed in the polyrotaxanes described herein. For example, the cyclic molecule may be a crown ether, cucurbituril [n] uryl, calixarene, cyclic amide and / or transition metal complex. However, in some particularly preferred embodiments of the polyrotaxan of the present invention, the cyclic molecule is selected from the group consisting of cyclodextrins, cyclodextrin derivatives and any combination thereof. In one embodiment, the cyclic molecule is cyclodextrin. In another embodiment, the cyclic molecule is a cyclodextrin derivative. In some embodiments of polyrotaxane, cyclodextrin and cyclodextrin derivatives are used in combination.

In some embodiments of the polyrotaxane disclosed herein, the cyclodextrin or cyclodextrin derivative is a native cyclodextrin, a methylated cyclodextrin, an acetylated cyclodextrin, a hydroxyethylated cyclodextrin, a hydroxypropylated cyclodextrin. , Cationic cyclodextrin derivatives, anionic cyclodextrin derivatives, glucosylated cyclodextrins, chemically reactive cyclodextrin derivatives, and any combination thereof. In a further embodiment, the cyclodextrin or cyclodextrin derivative is α-cyclodextrin, randomly methylated α-cyclodextrin, β-cyclodextrin, randomly methylated β-cyclodextrin (RAMEB), hydroxypropyl. β-Cyclodextrin, acetyl β-cyclodextrin, heptaxis (2,6-di-O-methyl) -β-cyclodextrin, carboxymethyl-β-cyclodextrin, succinyl-β-cyclodextrin, (2-carboxyethyl) -Β-Cyclodextrin, β-cyclodextrin, sulfobutylated β-cyclodextrin, β-cyclodextrin sulfate, 6-monodeoxy-6 monoamino-β-cyclodextrin hydrochloride, heptax-6-deoxy-6-amino) -Β-Cyclodextrin, (2-hydroxy-3-N, N, N-trimethylamino) propyl-β-cyclodextrin, heptaxis (2,6-tri-O-methyl) -β-cyclodextrin, mono-amino -Β-Cyclodextrin, sulfobutyl-β-cyclodextrin, γ-cyclodextrin, randomly methylated γ-cyclodextrin, 2-hydroxy-3-N, N, N-trimethylaminopropyl-β-cyclodextrin halogen It is selected from the group consisting of compounds, any salt thereof, and any combination thereof. In a further embodiment, the cyclodextrin or cyclodextrin derivative is a sodium carboxymethyl-α-cyclodextrin salt, a sodium carboxymethyl-β-cyclodextrin salt, succinyl-α-cyclodextrin, succinyl-β-cyclodextrin, succinyl. -Γ-Cyclodextrin, (2-carboxyethyl) -α-cyclodextrin, (2-carboxyethyl) -β-cyclodextrin, α-cyclodextrin sodium salt, β-cyclodextrin sodium salt, γ- Sodium cyclodextrin phosphate, sulfobutylated β-cyclodextrin sodium salt, sulfobutylated β-cyclodextrin sodium salt, sulfobutylated β-cyclodextrin sodium salt, α-cyclodextrin sodium sulfate salt, β-cyclodextrin sodium sulfate salt, γ-Cyclodextrin sodium sulfate, 6-monodeoxy-6-monoamino-β-cyclodextrin hydrochloride, heptaxis (6-deoxy-6-amino) -β-cyclodextrin heptachloride, octakis (6-deoxy-6) An ion selected from the group consisting of -amino) -γ-cyclodextrin octahydrochloride, (2-hydroxy-3-N, N, N-trimethylamino) propyl-β-cyclodextrin chloride, and any combination thereof. It is a sex cyclodextrin or an ionic cyclodextrin derivative. In certain preferred embodiments, the cyclodextrin derivative is a randomly methylated β-cyclodextrin (RAMEB).

As long as the first monomer has a stopper group with sufficient steric bulk to block the mobility of the cyclic molecule along the copolymer and to prevent the cyclic molecule from decomposing from the copolymer chain. The first monomer is not particularly limited. Preferably, the first monomer having a stopper group is a vinyl monomer. The term "vinyl monomer" also, when used with respect to the polyrotaxans described herein, generally refers to a monomer having a vinyl group. In this regard, the term "vinyl group" refers to the group-CH = CH ₂ . Optionally, the vinyl group can carry one or more substituents instead of any one of the hydrogen atoms (eg, methyl group in poly (ethylene glycol) methacrylate). Preferably, the first monomer has a molecular weight of 70 g / mol or more. Therefore, in some embodiments of polyrotaxane, the first monomer having a stopper group has a molecular weight of 70 g / mol to 1000 g / mol, preferably 100 g / mol to 500 g / mol.

In some embodiments of the polyrotaxane disclosed herein, the first monomer is milsen, an aromatic vinyl monomer, N-isopropyl (meth) acrylamide, N-vinylcaprolactam, N-vinylimidazole, poly ( It is selected from the group consisting of ethylene glycol) (meth) acrylate, α, ω-bis (meth) acrylate, and any combination thereof. When the first monomer is poly (ethylene glycol) (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is preferably 3000 g / mol or less. More preferably, when the first monomer is poly (ethylene glycol) (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is 1000 g / mol or less. In certain embodiments, the first monomer is poly (ethylene glycol) methyl ether (meth) acrylate. In certain embodiments, the first monomer is hydroxyethyl (meth) acrylate. In some embodiments where the first monomer having a stopper group is an aromatic vinyl monomer, the aromatic vinyl monomer is optionally substituted styrene, optionally substituted styrene sulfonic acid, optionally substituted. It is selected from the group consisting of vinylpyridines, optionally substituted divinylbenzenes, and any combination thereof. The term "sometimes substituted" is mentioned in the context of occasionally substituted styrene, sometimes substituted styrene sulfonic acid, sometimes substituted vinylpyridine and sometimes substituted divinylbenzene. If so, it is independently selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl, C1-C10 haloalkyl, C1-C10 alkoxy, CN, nitro, halogen (F, Cl, Br, I) and the like. Represents one or more substituents to be made. In one embodiment, the aromatic vinyl monomer is 4- (trifluoromethyl) styrene. When α, ω-bis (meth) acrylate is used, in embodiments, the α, ω-bis (meth) acrylate is ethylene glycol, oligoethylene glycol, poly (ethylene glycol), bisphenol A and any of them. Α, ω-bis (meth) glycolate of the mixture of. When the α, ω-bis (meth) acrylate is a poly (ethylene glycol) α, ω-bis (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is preferably 3000 g / mol or less. More preferably, when the α, ω-bis (meth) acrylate is a poly (ethylene glycol) α, ω-bis (meth) acrylate, the molecular weight of the poly (ethylene glycol) unit is 1000 g / mol or less.

With respect to the polyrotaxans described herein, and as long as the second monomer can form a compartment of the copolymer having a substantially linear structure, the second monomer is not particularly limited. Therefore, the second monomer may be a substantially linear monomer. As mentioned above, the term "substantially linear" does not preclude the branching of such compartments (so that the cyclic molecule is rotatable and exhibits mobility along the compartment). As long as a compartment with a linear structure can penetrate the cyclic molecule). As a result, the second monomer may be branched, preferably slightly branched, as long as the branch does not prevent the rotation of the cyclic molecule and the mobility of the cyclic molecule along the copolymer. Preferably, the second monomer is a vinyl monomer. More preferably, both the first monomer and the second monomer having a stopper group are vinyl monomers. Preferably, in any one of the methods disclosed herein, the second monomer has a molecular weight of 120 g / mol or less, more preferably 110 g / mol or less.

In the polyrotaxans described herein, the second monomer is a nonionic monomer. In some embodiments, the second monomer is a hydrophobic monomer, especially a nonionic hydrophobic monomer. As used herein in the context of any one of the polyrotaxans, the term "hydrophobic monomer" refers to a monomer that is insoluble in water or simply sparingly soluble in water. For the purposes of the polyrotaxans described herein, the hydrophobic monomers are preferably less than 20 g / l, more preferably less than 10 g / l, even more preferably less than 5 g / l in water at 20 ° C. And most preferably it has a solubility of less than 2 g / l. Hydrophobic monomers are particularly preferred when cyclodextrins or cyclodextrin derivatives are used. In some embodiments, the second monomer is selected from the group of vinyl monomers having a molecular weight of less than 120 g / mol. Preferably, the second monomer is selected from the group of vinyl monomers having a molecular weight less than 110 g / mol. Additional or alternative, in some embodiments, the second monomer is 1,3-diene, 1,3,5-triene, (meth) acrylate, vinyl ester, vinyl-ether, (meth). It is selected from the group of vinyl monomers consisting of acrylonitrile, (meth) acrylic acid, (meth) acrylamide, and any combination thereof. When the second monomer is 1,3-diene, the 1,3-diene is preferably selected from 1,3-butadiene, derivatives of 1,3-butadiene, isoprene, and any combination thereof. To. Therefore, in one embodiment, 1,3-butadiene is used. In one embodiment, isoprene is used. In another embodiment, 1,3-butadiene and isoprene are used in combination. In one embodiment, 1,3-diene is dimethyl butadiene. When the second monomer is a vinyl ester, in some embodiments the vinyl ester is vinyl acetate. When the second monomer is a vinyl ether, in some embodiments, the vinyl ether is a methyl-vinyl ether. When the second monomer is (meth) acrylate, the (meth) acrylate is selected from the group consisting of methylacryllate, methylmethacrylate and any combination thereof. Therefore, in one embodiment, the second monomer is methylacryllate. In one embodiment, the second monomer is methylmethacrylate. In another embodiment, methylacryllate and methylmethacrylate are used in combination.

According to embodiments, the nonionic copolymer of any polyrotaxane described herein may be a hydrophobic copolymer, as the hydrophobic monomer may be used as the second monomer. For the purposes of the present disclosure, "hydrophobic copolymers" are structural units derived from at least 60 mol% hydrophobic monomers, preferably at least 70 mol% hydrophobic, based on a total of 100 mol% of the total structural units of each copolymer. Structural units derived from monomers, more preferably at least 80 mol% of hydrophobic monomers, even more preferably at least 90 mol% of hydrophobic monomers, and most preferably at least 95 mol. May be defined as a copolymer containing structural units derived from% hydrophobic monomers. In this context, the term "hydrophobic monomer" is defined as above, ie, a monomer that is insoluble in water or sparingly soluble in water. Preferably, the hydrophobic monomer has a solubility of less than 20 g / l, more preferably less than 10 g / l, even more preferably less than 5 g / l, and most preferably less than 2 g / l in water at 20 ° C. These definitions of hydrophobic monomers may apply to both the first and second monomers having a stopper group. When cyclodextrin and / or cyclodextrin derivatives are used, it is preferred that the polyrotaxane copolymers described herein are hydrophobic copolymers. Cyclodextrins and cyclodextrin derivatives have hydrophobic cavities, so passing cyclodextrin and / or cyclodextrin derivatives over hydrophobic copolymers results in only small interactions between the copolymers and cyclic molecules. Due to such small interactions, the rotatability of the cyclic molecule and its mobility along the copolymer chain are not significantly impaired.

In one preferred embodiment of any one of the polyrotaxans disclosed herein, the first monomer having a stopper group is poly (ethylene glycol) methyl ether methacrylate and the second monomer is isoprene. , And the cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). In addition, in this embodiment, randomly methylated β-cyclodextrin (RAMEB) and 2-hydroxy-3-N, N, N-trimethylamino) propyl-β-cyclodextrin chloride (cationic cyclic molecule). May be used in combination. These combinations of monomers and cyclic molecules may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer. Polyrotaxanes with this combination of monomers and cyclic molecules have been found to be water soluble and soluble or dispersible in organic solvents such as tetrahydrofuran, dimethyl sulfoxide or chloroform.

In another preferred embodiment of any one of the polyrotaxans as described herein, the first monomer having a stopper group is styrene, the second monomer is isoprene, and the cyclic molecule. Is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomer and cyclic molecule may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer. Polyrotaxanes with this combination of monomers and cyclic molecules have been found to be soluble in organic solvents such as tetrahydrofuran or chloroform.

In another preferred embodiment of any one of the polyrotaxans disclosed herein, the first monomer having a stopper group is myrcene, the second monomer is isoprene, and the cyclic molecule is. It is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomers and cyclic molecules may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer or a block copolymer. Polyrotaxanes with this combination of monomers and cyclic molecules have been found to be soluble in organic solvents such as tetrahydrofuran or chloroform.

In another preferred embodiment of any one of the polyrotaxans as described herein, the first monomer having a stopper group is a poly (ethylene glycol) monomethacrylate (PEGMA) and the second monomer. Is isoprene, and the cyclic molecule is selected from cyclodextrins, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomer and cyclic molecule may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer. Polyrotaxanes with this combination of monomers and cyclic molecules have been found to be soluble in water and in organic solvents such as tetrahydrofuran, dimethyl sulfoxide or chloroform.

In another preferred embodiment of any one of the polyrotaxans as described herein, the first monomer having a stopper group is styrene, the second monomer is methylacrylate, and The cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomer and cyclic molecule may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer.

In another preferred embodiment of any one of the polyrotaxans as described herein, the first monomer having a stopper group is a poly (ethylene glycol) methyl ether methacrylate and the second monomer is. It is dimethyl butadiene, and the cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is a randomly methylated β-cyclodextrin (RAMEB). This combination of monomer and cyclic molecule may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer.

In another preferred embodiment of any one of the polyrotaxans as described herein, the first monomer having a stopper group is hydroxyethyl methacrylate, the second monomer is isoprene, and , The cyclic molecule is selected from cyclodextrin, cyclodextrin derivatives and any combination thereof. Preferably, in this embodiment, the cyclic molecule is β-cyclodextrin. This combination of monomer and cyclic molecule may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer.

In another preferred embodiment of any one of the polyrotaxans as described herein, the first monomer having a stopper group is poly (ethylene glycol) methyl ether methacrylate, and the second monomer is. It is an isoprene, and the cyclic molecule is a hydroxyproylated cyclodextrin. Preferably, in this embodiment, the cyclic molecule is hydroxypropyl-β-cyclodextrin. This combination of monomer and cyclic molecule may be used in any of the polyrotaxans described herein where the copolymer is a random copolymer.

Any embodiments, features, definitions, etc. described herein that are referred to for any method of preparing polyrotaxane are also applicable mutatis mutandis to any polyrotaxane described herein. Similarly, any embodiments, features, definitions, etc. described herein that are referred to for any polyrotaxan also apply mutatis mutandis to any method of preparing the polyrotaxane described herein.

As an advantage, the polyrotaxanes of the present invention are soluble or dispersible in water or in organic solvents (used in industries such as tetrahydrofuran, dichloromethane, chloroform, ethyl acetate and acetone). Therefore, the treatment of polyrotaxane for various uses can be easily achieved.

In some embodiments, the polyrotaxane is dispersed in water to form an aqueous dispersion. Therefore, the present invention also relates to an aqueous dispersion containing the polyrotaxane of the present invention dispersed in water. In certain embodiments, the dispersed polyrotaxane has a particle size of 5 μm or less.

In some embodiments, the polyrotaxane is dissolved in water to form an aqueous solution. Therefore, the present invention also relates to an aqueous solution containing the polyrotaxane of the present invention dissolved in water.

The present invention also relates to a method for preparing a crosslinked polyrotaxane, which comprises (a) a step of providing the polyrotaxane of the present invention and (b) a step of chemically or physically crosslinking the polyrotaxane.

In some embodiments of the method of preparing a crosslinked polyrotaxane, the cross-linking is a molecule of polyrotaxane by cross-linking the cyclic molecule using a cross-linking agent having at least two functional groups capable of forming a bond to the cyclic molecule. Including cross-linking. In one particularly preferred embodiment, such intermolecular cross-linking of polyrotaxane is a first cyclic molecule threaded over the first copolymer chain and a second cyclic molecule threaded over another second copolymer chain. Includes forming a co-link with. Cross-linking may be performed under heating in any one of the methods described herein for preparing cross-linked polyrotaxanes. In a preferred embodiment of the method of preparing a crosslinked polyrotaxane, the cyclic molecule is a cyclodextrin or cyclodextrin derivative, and the crosslinking agent forms a bond with the functional group of the cyclodextrin or cyclodextrin derivative. It has at least two possible functional groups. In certain preferred embodiments, the functional group of the cyclodextrin or cyclodextrin derivative that reacts with the cross-linking agent is a hydroxyl group. In some embodiments, the cross-linking agent is selected from the group consisting of diisocyanate, block diisocyanate, diisocyanate, bisepoxide, cyanuric chloride, divinyl sulfone, and any combination thereof. Block diisocyanates can be referred to as reaction products formed from diisocyanates that are stable at room temperature but dissociate under the influence of heating to regenerate the isocyanate functionality. If the cross-linking agent is block diisocyanate, block diisocyanate described in D.A. Wicks, Z.W. Wicks Jr, Prog. Org. Coatings 1999, 36, 148-172 may be used. When the cross-linking agent is bisepoxide, the bisepoxide may be bisphenol-A diglycidyl ether. However, the cross-linking agent is not particularly limited, and those skilled in the art may appropriately select other suitable cross-linking agents. In an embodiment, the method of preparing a crosslinked polyrotaxane provides a gel. In a particularly preferred embodiment, the gel is a ring gel.

The present invention also relates to a crosslinked polyrotaxane in which the polyrotaxan of the present invention is chemically or physically crosslinked.

In a preferred embodiment, the crosslinked polyrotaxane can or is obtained by any method of preparing the crosslinked polyrotaxane described herein according to the present invention.

In some embodiments of crosslinked polyrotaxane, the polyrotaxane is intermolecularly crosslinked via a cyclic molecule and a crosslinking agent. In one particularly preferred embodiment, such intermolecular cross-linking of polyrotaxane is a first cyclic molecule threaded over the first copolymer chain and a second cyclic molecule threaded over another second copolymer chain. Provided by a shared connection with. In some embodiments, the cyclic molecule is a cyclodextrin or cyclodextrin derivative, and the cross-linking agent is attached to the functional group of the cyclodextrin or cyclodextrin derivative. In certain preferred embodiments, the functional group of the cyclodextrin or cyclodextrin derivative that reacts with the cross-linking agent is a hydroxyl group. In some embodiments, the cross-linking agent is selected from the group consisting of diisocyanate, block diisocyanate, diisocyanate, bisepoxide, cyanuric chloride, divinyl sulfone, and any combination thereof. If the cross-linking agent is block diisocyanate, block diisocyanate described in D.A. Wicks, Z.W. Wicks Jr, Prog. Org. Coatings 1999, 36, 148-172 may be used. When the cross-linking agent is bisepoxide, the bisepoxide may be bisphenol-A diglycidyl ether. However, the cross-linking agent is not particularly limited, and those skilled in the art may appropriately select other suitable cross-linking agents.

In some embodiments, the crosslinked polyrotaxane is a gel. In this regard, the crosslinked polyrotaxane can form a physical or chemical gel. As is known to those skilled in the art, physical gels are non-covalently crosslinked due to physical gravitational effects between polymers such as ion interactions, hydrophobic interactions, hydrogen bonds, microcrystal formation, helix formation, etc. Has a joint. On the other hand, in chemical gels, cross-linking is provided through covalent bonds.

In a particularly preferred embodiment, the crosslinked polyrotaxane is a ring gel. Ringing gels differ from physical and chemical gels because the polymer chains are phase-linked in the ringing gel. In ring gels, almost only cyclic molecules are cross-linked, but copolymer chains are not or only slightly cross-linked. More specifically, as can be seen from FIG. 2, which graphically depicts the formation of the ring gel and the ring gel according to the embodiment of the present invention, the ring gel is passed over the first copolymer chain. Demonstrates an architecture in which the first cyclic molecule is co-linked to a second cyclic molecule threaded over another second copolymer chain. By such cross-linking, the two cyclic molecules co-linked to each other exhibit a shape resembling a figure eight. Since only the cyclic molecule is cross-linked, the cross-link is freely mobile along the copolymer chain and thus is free to move in the polymer network. As a result, the tension of the copolymer chain penetrating the cyclic molecule is equalized as in the pulley. This effect automatically disperses the tension in the copolymer chain against tensile deformation and is therefore less likely to cause cracks or defects. The concept of ring gel is described, for example, in K. Ito, Polym. J. (Tokyo, Jpn.) 2007, 39, 489-499.

Any embodiments, features, definitions, etc. described herein that are referred to for any method of preparing a crosslinked polyrotaxane are also referred to in any crosslinked polyrotaxane described herein. Apply mutatis mutandis. Similarly, any method, feature, definition, etc. described herein that is referred to for any cross-linked polyrotaxane is also any method of preparing the cross-linked polyrotaxane described herein. Applies mutatis mutandis to.

The polyrotaxane and crosslinked polyrotaxane disclosed herein are used as self-healing materials, for encapsulation, for drug delivery, for the preparation of solutions, dispersions or mixed materials, as adhesives, and for surface coatings. It may be used as an agent.

Therefore, also included by the present invention is the use of polyrotaxane as disclosed herein as a self-healing material. In addition, the invention also relates to the use of crosslinked polyrotaxane as disclosed herein as a self-healing material. Accordingly, the present invention is also a method of providing a surface having a self-healing surface coating, wherein (a) the steps of providing the surface and (b) the polyrotaxane and / or cross-linking disclosed herein on the surface. The present invention relates to a method comprising a step of coating a crosslinked polyrotaxane to provide a surface having a self-healing surface coating. For application as a self-healing material, it is particularly preferred that polyrotaxane is a ring gel. The surface is not particularly limited, and for example, the surface may be a metal surface, a glass surface, a ceramic surface, a wood surface, or the like. In this regard, the term "self-healing" refers to the ability of a material to repair damage caused by mechanical impact without human intervention. Self-healing properties are useful, for example, in paints and adhesives. Such paints and adhesives are used not only for automatic propulsion vehicles that require car wash resistance, chipping resistance, impact resistance and weather resistance, but also for paints for home electric appliances, resin substrates and the like. Can be used.

The present invention further relates to the use of polyrotaxane as disclosed herein for encapsulation. The present invention also relates to the use of crosslinked polyrotaxanes for encapsulation as disclosed herein. Accordingly, the present invention is also a method of encapsulating a material with polyrotaxane, wherein (a) a step of providing the material to be encapsulated, and (b) the polyrotaxane and / / the material disclosed herein. Alternatively, the present invention relates to a method including a step of encapsulating using crosslinked polyrotaxane to provide an encapsulated material. In embodiments, the polyrotaxane or crosslinked polyrotaxane is used for encapsulation of a pharmaceutically active agent. This means that the material to be encapsulated is a pharmaceutically active agent. The pharmaceutically active agent to be encapsulated with polyrotaxane or crosslinked polyrotaxane is not particularly limited. For example, in embodiments, the pharmaceutically active agent is selected from the group consisting of hydrophobic drugs, steroidal drugs, anti-cancer drugs, and any combination thereof.

Furthermore, the present invention relates to the use of polyrotaxane as described herein as a carrier for pharmaceutically active agents. Similarly, the invention also relates to the use of crosslinked polyrotaxane as described herein as a carrier for pharmaceutically active agents. The pharmaceutically active agent to be encapsulated with polyrotaxane or crosslinked polyrotaxane is not particularly limited. For example, in embodiments, the pharmaceutically active agent is selected from the group consisting of hydrophobic drugs, steroidal drugs, anti-cancer drugs, and any combination thereof.

The present invention also relates to a method of coating a surface with polyrotaxane, which comprises coating the surface with a solution or dispersion containing polyrotaxane as described herein. In some embodiments, the coating is carried out using dipping, spin coating, spraying, and / or spray coating. Preferably, the coating is carried out using a dispersion or solution of polyrotaxane in water or in an organic solvent. The surface to be coated is not particularly limited. For example, the surface to be coated may be a metal surface, a glass surface, a ceramic surface, a wood surface, or the like. Such methods can be used, for example, to apply a self-healing coating of polyrotaxane to the surface. The coating agents containing polyrotaxane described herein are useful, for example, as corrosion inhibitors for controlling adhesion and friction and for providing scratch resistance.

Also included by the present invention is the use of crosslinked polyrotaxane as described herein as an adhesive. Preferably, if the crosslinked polyrotaxane is used as an adhesive, the crosslinked polyrotaxane is a gel.

The present invention further relates to a dispersion containing metal particles and / or metal oxide particles and polyrotaxane as described herein. In some embodiments, the metal particles and / or metal oxide particles are nanoparticles.

The present invention also relates to a complex composed of metal particles and / or metal oxide particles and polyrotaxane as described herein. In some embodiments, the metal particles and / or metal oxide particles are nanoparticles.

As used herein, it should be noted that the singular forms "a", "an", and "the" include plural referents unless explicitly stated in the context. Is. Thus, for example, a reference to "a reagent" comprises one or more such different reagents, and a reference to "the method" is described herein. Includes references to equivalent steps and methods known to those of skill in the art that can alter or replace the method.

All publications and patents cited in this disclosure are incorporated by reference in their entirety. To the extent that the materials incorporated by reference are inconsistent or inconsistent with the specification, the specification will supersede any such material.

Unless otherwise indicated, the term "at least" preceding a set of elements should be understood to refer to all of the set of elements. One of ordinary skill in the art will recognize or confirm using a few routine experiments a number of equivalents to a particular embodiment of the invention described herein. Such equivalents are intended to be included in the present invention.

Throughout the specification and the claims below, unless contextually requires otherwise, the words "comprise" and variants such as "comprises" and "comprising" are specified integers. Alternatively, it may be understood that it is intended to include a process or integer or group of steps, but not to exclude any other integer or process or group of integers or processes. As used herein, the term "comprising" can be replaced by the term "containing", or often as used herein. It can be replaced by the term "having".

As used herein. "Consisting of" excludes any element, process, or component not specified in the elements of the claims. As used herein, "consisting essentially of" does not exclude materials or processes that do not substantially affect the fundamental and novel features of the claims. In each case herein, any one of the terms "comprising", "consisting essentially of" and "consisting of" is the other two. It may be replaced with any of the terms.

Several references are cited throughout the text of this specification. Each of the references cited herein (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions for use, etc.), whether above or below, is in its entirety by reference. Incorporated into the specification. It should not be construed herein to acknowledge that the invention is not entitled to precede such disclosure by prior invention.

The following examples further illustrate the invention. However, these examples should not be construed as limiting the scope of the invention. The examples are included for illustrative purposes, and the invention is limited only by the claims.

Example 1
Polyrotaxane prepared via free radical polymerization: poly (isoprene-co-PEG methyl ether methacrylate) -randomly methylated β-cyclodextrin polyrotaxane

Ammonium persulfate (radical initiator) 6.50 mg (0.03 mmol), randomly methylated β-cyclodextrin (RAMEB, cyclic molecule) 5.90 g (4.50 mmol) and poly (ethylene glycol) methyl ether methacrylate 0.22 g (0.45 mmol) of (first monomer having a stopper group) was dissolved in 10 mL of deionized water, and nitrogen gas was bubbled into the system for 30 minutes with stirring. After the addition of 0.45 mL (0.31 g, 4.50 mmol) of freshly distilled isoprene (second monomer, hydrophobic), the nitrogen flow was stopped and the system was stirred to give a homogeneous solution. (That is, RAMEB / isoprene complex formation). The reaction was initiated by the addition of a catalytic amount (<0.1 mL) of N, N, N', N'-tetramethylethylenediamine (TMEDA) and stirred at room temperature for several hours. After the reaction, a clear aqueous solution was purified by ultrafiltration (10000 molecular weight cutoff polyether sulfone membrane). After lyophilization, the product (500 mg) was obtained as a white powder.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0, no trace of free RAMEB
^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 ppm (methyl group) ) (About polyisoprene), 5.00 (s, 1H, H-1), 3.65 (s, 3H, H-7), 3.40 (s, 3H, H-8), 3.95- 3.25 (m, 5H, H-2, H-3, H-4, H-5, H-6) ppm (about RAMEB)
Optical rotation measurement: c = 3.40 mg / mL α = 0.036 deg
ITC: Free RAMEB 7.5wt%

In the isothermal titration calorimetry (ITC) study of polyrotaxane prepared in Example 1, the sample was only 6.4 free, randomly methylated β-cyclodextrin (RAMEB) not passed over the isoprene styrene copolymer. Indicates that it contains%.

Example 2
Polyrotaxane prepared via free radical polymerization: poly (isoprene-co-styrene) -randomly methylated β-cyclodextrin polyrotaxan

Ammonium persulfate (radical initiator) 6.50 mg (0.03 mmol), randomly methylated β-cyclodextrin (RAMEB, cyclic molecule) 5.90 g (4.50 mmol) and styrene (first with stopper group) 0.046 mL (0.45 mmol) of (monomer) was dissolved in 10 mL of deionized water and the system was bubbled with nitrogen gas for 30 minutes with stirring. After the addition of 0.45 mL (0.31 g, 4.50 mmol) of freshly distilled isoprene (second monomer, hydrophobic), the nitrogen flow was stopped and the system was stirred to give a homogeneous solution. (That is, RAMEB / isoprene complex formation). The reaction was initiated by the addition of a catalytic amount (<0.1 mL) of N, N, N', N'-tetramethylethylenediamine (TMEDA) and stirred at room temperature for several hours. After the reaction, the product was filtered off and lyophilized overnight. The product (300 mg) was obtained as a white foam.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0, no trace of free RAMEB
^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 ppm (methyl group) ) (About polyisoprene), 5.00 (s, 1H, H-1), 3.65 (s, 3H, H-7), 3.40 (s, 3H, H-8), 3.95- 3.25 (m, 5H, H-2, H-3, H-4, H-5, H-6) ppm (for RAMEB) and 7.10-7.50 ppm (for aromatic protons of styrene)
Optical rotation measurement: c = 0.98 mg / mL α = 0.007 deg
ITC: Free RAMEB 6.4wt%

A small amount (20-50 mg) of polyrotaxane was reacted with HClO ₄ (1 mM, 25 mL) at 70 ° C. for 20 hours. After neutralizing the acid with NaOH, the resulting insoluble polymer was removed from the aqueous phase by filtration, washed several times with water and dried under vacuum.

FIG. 3 penetrates a randomly methylated β-cyclodextrin (RAMEB) obtained by hydrolysis of a) polyrotaxane prepared in Example 2 and b) polyrotaxane prepared as described above. not showing the ¹ H NMR spectrum of free isoprene styrene copolymer. The signal spread in a) indicates a polyrotaxane structure in which randomly methylated β-cyclodextrin was passed over an isoprene styrene copolymer.

FIG. 4 shows the ROESY NMR spectrum in CDCl _{3 of} the polyrotaxane prepared in Example 2. The highlighted cross-peaks show the correlation between the olefin protons of the isoprene styrene copolymer and the protons of the randomly methylated β-cyclodextrin (RAMEB), which allows the RAMEB to pass over the copolymer. It suggests that there is.

Example 3
Statistical Copolymers Prepared Through Reversible Addition-Cleavage Chain Transfer Radical Copolymerization (RAFT) Polyrotaxane: Poly (Isoprene-co-myrcene) -Randomly Methylated β-Cyclodextrin Polyrotaxane

2,2'-Azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride (Wako Pure Chemical Industries, Ltd. initiator VA-044) 0.92 mg (0.003 mmol), S, S '-Bis (α, α'-dimethyl-α''-acetic acid) -trithiocarbonate (chain transfer agent) 8.06 mg (0.03 mmol), randomly methylated β-cyclodextrin (RAMEB, cyclic) Molecules) 5.90 g (4.50 mmol) and Milsen (first monomer having a stopper group) 0.08 mL (61 mg, 0.45 mmol) were dissolved in 10 mL of deionized water and nitrogen was added to the system under stirring. The gas was bubbling for 30 minutes. After the addition of 0.45 mL (0.31 g, 4.50 mmol) of freshly distilled isoprene (second monomer, hydrophobic), the nitrogen flow was stopped and the system was stirred to give a homogeneous solution. (That is, RAMEB / isoprene complex formation). The reaction was placed in an oil bath at 35 ° C. and stirred for 3 days to initiate the reaction. In particular, the reaction vessel was heated to 35 ° C. and stirred for 3 days to initiate the reaction. After the reaction, the product was filtered off and dried under vacuum at 45 ° C. overnight. The product (250 mg) was obtained as a yellowish / clear oily film.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0, no trace of free RAMEB
^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 ppm (methyl group) ) (About polyisoprene), 5.00 (s, 1H, H-1), 3.65 (s, 3H, H-7), 3.40 (s, 3H, H-8), 3.95- 3.25 (m, 5H, H-2, H-3, H-4, H-5, H-6) ppm (about RAMEB)
Optical rotation measurement: c = 10.75 mg / mL α = 0.024 deg
ITC: Free RAMEB 2.2wt%

Example 4
Block Copolymers Polyrotaxane Prepared Through Reversible Addition-Cleavage Chain Transfer Radical Copolymerization (RAFT): Poly (Myrcene-b-Isoprene-b-Myrcene) -Randomly Methylated β-Cyclodextrin Polyrotaxane

2,2'-Azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride (Wako Pure Chemical Industries, Ltd. initiator VA-044) 0.92 mg (0.003 mmol), S, S '-Bis (α, α'-dimethyl-α''-acetic acid) -trithiocarbonate (bifunctional chain transfer agent) 8.06 mg (0.03 mmol), randomly methylated β-cyclodextrin ( Dissolve 0.59 g (0.45 mmol) of RAMEB, cyclic molecule) and 0.08 mL (61 mg, 0.45 mmol) of milsen (first monomer having a stopper group) in 1 mL of deionized water, and stir in the system. Underneath, nitrogen gas was bubbled for 30 minutes. The reactants were placed in an oil bath at 35 ° C. to initiate the reaction. In particular, the reaction vessel was heated to 35 ° C. to initiate the reaction and the reaction mixture was stirred. After a reaction time of 1 day, 0.45 mL (0.31 g, 4.50 mmol) of freshly distilled isoprene (second monomer, hydrophobic) complexed with 5.90 g (4.50 mmol) of RAMEB in 10 mL of water was added. It was added to the mixture and reacted for an additional 3 days. After the reaction, the turbid aqueous dispersion was heated above 80 ° C. The product precipitated at this temperature was filtered off and washed with warm water several times. After drying under vacuum at 45 ° C. overnight, the product (350 mg) was obtained as a yellowish / clear oily film.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0, no trace of free RAMEB
^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 ppm (methyl group) ) (About polyisoprene), 5.00 (s, 1H, H-1), 3.65 (s, 3H, H-7), 3.40 (s, 3H, H-8), 3.95- 3.25 (m, 5H, H-2, H-3, H-4, H-5, H-6) ppm (about RAMEB)
Optical rotation measurement: c = 2.00 mg / mL α = 0.006 deg
ITC: Free RAMEB <1wt%

Example 5
Statistical Copolymer Polyrotaxane Prepared Through Atom Transfer Radical Polymerization (ATRP): Poly (Isoprene-co-PEGMA) -Randomly Methylated β-Cyclodextrin Polyrotaxane

Randomly methylated β-cyclodextrin (RAMEB, cyclic molecule) 5.89 g (4.45 mmol), isoprene (second monomer, hydrophobic) 406 μl (4.06 mmol), poly (ethylene glycol) monomethacrylate Deionized water (PEGMA, first monomer with stopper group) 208 μl (0.45 mmol) and 2-hydroxyethyl 2-bromoisoprenelate (HEBIB, initiator for ATRP) 8.24 μl (0.06 mmol). It was dissolved in 8 ml. 35 mg (2.19 μmol) of hemoglobin (oxidoreductase, catalyst for ATRP) is dissolved in 3 ml of deionized water, and 15 mg (85.17 μmol) of ascorbic acid (reducing agent for catalyst regeneration) is dissolved in 2 ml of deionized water. Dissolved in. Nitrogen gas was bubbled into these three systems under stirring for 3 hours. Polymerization was initiated by transferring 2 ml of ascorbic acid solution and 3 ml of natural hemoglobin solution to a monomer flask, and the mixture was stirred at room temperature for 2 days. After the reaction, the solution was ultrafiltered through a 10 kDa cellulose-membrane and lyophilized. A brownish powder (285 mg) was obtained.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0.06
^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 ppm (methyl group) ) (About polyisoprene), 5.00 (s, 1H, H-1), 3.65 (s, 3H, H-7), 3.40 (s, 3H, H-8), 3.95- 3.25 (m, 5H, H-2, H-3, H-4, H-5, H-6) ppm (about RAMEB)
Optical rotation measurement: c = 10.30 mg / mL α = 0.090 deg
ITC: Free RAMEB 2.2wt%

FIG. 5 shows a DOSY NMR spectrum in CDCl _{3 of} polyrotaxane prepared in Example 5, in which randomly methylated β-cyclodextrin (RAMEB) is passed over an isoprene PEGMA copolymer. It suggests that it is. DOSY is depicts ¹ H- spectrum of conventional sample with attribution on the spectrum, the spectrum, RAMEB signal (3.95-3.25 and 5.00 ppm), polyisoprene signal (1.6,2 It shows 0.0 and 5.1 ppm) and PEGMA signal (3.65 ppm). The corresponding cross peaks are all positioned with a lower diffusion coefficient D of log D = −9.7 (corresponding to D = 2 × 10 ⁻¹⁰ m ² / s), which means that all components are the same. It suggests that it is part of the molecular entity, polyrotaxane. In contrast, free RAMEB is (corresponding to ^{D = 8 × 10 -10 m 2} / s) log D = -9.1 will have a pronounced high diffusion coefficient before and after.

FIG. 6 provides an isothermal titration calorimetry (ITC) measurement of the polyrotaxane at 25 ° C. (using the Nano ITC from TA Instruments), which is a free, randomly methylated β-cyclodextrin. It shows that (RAMEB) is almost absent in the sample. The total weight fraction _{w oT} of RAMEB of the polyrotaxane, RAMEB [α] = + 130 obtained from the applied Perkin Elmer Model 241 polarimeter the specific rotation of the solution in CHCl ₃ at α = 589nm (10mg / ml ) Was determined from the optical rotation. A solution of the polyrotaxane in 0.1 M phosphate buffer (total RAMEB concentration 1.0 mM) was titrated with an 8 mM solution of guest adamantan-1-carboxylic acid sodium salt monitored by ITC. The heat generated was corrected by the corresponding heat of dilution and adapted to the TA Instruments NanoAnalyze program using an algorithm for interaction in 1: 1 stoichiometry. The observed stoichiometric number n = 0.021 means that 2.1 mol% of RAMEB was free. In other words, 97.9 mol% of RAMEB was not available to the guest because it was passed over the polyisoprene chain. The weight fraction w ₀ of the penetrated RAMEB was calculated according to w ₀ = w _oT (1-n). The weight fraction of the penetrating polymer is equal to the sum of the weight fractions of monomer 1 and monomer 2 (w ₁ + w ₂ = 1-w ₀ ). The ratio of w ₁ to w ₂ was determined from the integral ratio of each ¹ H NMR signal normalized to each respective proton number. The mole fractions x _i of RAMEB and monomer units 1 and 2 are as follows:

According to RAMEB, the molecular weights of monomer units 1 and 2, respectively, M ₀ , M ₁ and M ₂ are used for calculation.

Example 6
Statistical Copolymers Prepared Through Free Radical Polymerization Polyrotaxane: Poly (Isoprene-co-PEG Methyl Ether Methrate) -Randomly Methylated β-Cyclodextrin and (2-Hydroxy-3-N, N, N- Trimethylamino) propyl-β-cyclodextrin chloride polyrotaxane

Ammonium persulfate (radical initiator) 6.50 mg (0.03 mmol), randomly methylated β-cyclodextrin (RAMEB, cyclic molecule) 5.37 g (4.09 mmol), (2-hydroxy-3-N, N, N-trimethylamino) propyl-β-cyclodextrin chloride (cationic cyclic molecule) 0.63 g (0.41 mmol) and poly (ethylene glycol) methyl ether methacrylate (first monomer having a stopper group) 0 .22 g (0.45 mmol) was dissolved in 10 mL of deionized water and the system was bubbled with nitrogen gas for 30 minutes with stirring. After the addition of 1.80 mL (1.23 g, 18 mmol) of freshly distilled isoprene (second monomer, hydrophobic), the nitrogen flow was stopped and the system was stirred to give a homogeneous solution (ie). , RAMEB / isoprene complex formation). The reaction was initiated by the addition of a catalytic amount (<0.1 mL) of N, N, N', N'-tetramethylethylenediamine (TMEDA) and stirred at room temperature for several hours. After the reaction, a clear aqueous solution was purified by ultrafiltration (cellulose membrane with a 10000 molecular weight cutoff). After lyophilization, the product (300 mg) was obtained as a white powder.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0, no trace of free RAMEB
¹ H-NMR (DMSO d ₆ , 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 (methyl group) ) (For polyisoprene); 5.77 (s, 0.1H cationic group), 5.00 (s, 1H, H-1), 4.80 (s, 1H, H-7), 4. 50 (s, 1H-cationic group), 4.09 (s, 1H, cationic group), 3.50 (s, PEG), 3.40 (s, 3H, H-8), 3. 95-3.25 (m, 5H, H-2, H-3, H-4, H-5, H-6), 3.00 (0.4H, cationic group) ppm (for RAMEB) and (2-Hydroxy-3-N, N, N-trimethylamino) Propyl-β-cyclodextlinkolide Rotational measurement: c = 4.90 mg / mL α = 0.052 deg (in DMSO)
ITC: Free RAMEB 2.9wt%

Example 7
Cyclodextrin content of polyrotaxane obtained in Examples 1 to 5 The cyclodextrin content w _{0 of} polyrotaxane obtained in Examples 1 to 6 and the molar ratio of isoprene repeating unit to RAMEB unit x ₂ / x ₀ are set in Example 5. It was calculated according to the procedure shown in the description of FIG. 6 and listed in Table 1 below.

The values in Table 1 indicate that when the copolymerization is carried out as free radical polymerization or atom transfer radical polymerization (ATRP), a low ratio of isoprene repeating units to high content of penetrated cyclodextrin and cyclodextrin units is obtained. Is shown. On the other hand, when reversible additional cleavage chain transfer radical polymerization (RAFT polymerization) is employed, a relatively high ratio of isoprene units to the relatively low content of penetrated cyclodextrin and cyclodextrin units is obtained.

Example 8
Micelle formation test (Nile red fluorescence test)
In order to evaluate the compatibility of the polyrotaxane prepared in Examples 1 to 6 for micelle formation and encapsulation, an experiment of encapsulating the Nile red dye with polyrotaxane was carried out.

Nile Red (IUPAC name: 9-diethylamino-5-benzo [α] phenoxadinone) is widely used to determine the formation of micelles in aqueous solution or the solubilization of hydrophobic materials. This test considers that the UV-visible spectrum of Nile Red is strongly dependent on the environmental solubility of this dye. In other words, the absorption of UV and / or visible light of nitrile red is affected by the environment of the dye, and the Nile red molecules encapsulated inside the non-polar inside of the micelles or capsules are liberated in the aqueous solution. It shows absorption of UV / Vis irradiation, which is significantly different from the absorption of Nile red molecules.

The test was performed using different concentrations of Nile Red at 10 μM, 20 μM, 30 μM, 40 μM and 50 μM, while maintaining a constant concentration of polyrotaxane. Polyrotaxane and Nile Red were each dissolved separately in anhydrous tetrahydrofuran and then poured into water. Alternatively, if the polyrotaxane has a high cyclodextrin content, the polyrotaxane may be dissolved directly in water. To remove tetrahydrofuran, the resulting aqueous solution was stirred at room temperature for 3 days and the solution was refilled with water.

Aqueous solutions prepared according to this protocol were investigated using UV / Vis spectroscopy. Samples prepared from polyrotaxane and Nile Red showed a wide absorption band at 527 nm due to Nile Red in a non-polar environment. This result indicates that the Nile Red molecule is encapsulated inside the non-polar structure of the polyrotaxane moiety, i.e., the Nile Red is encapsulated with polyrotaxane. In contrast, no absorption was observed around 527 nm in the comparative Nile Red solution, which did not contain polyrotaxane. FIG. 7 shows the UV / Vis spectra of the Nile Red Dye (50 μM) in the presence and absence of a) and b) the polyrotaxane prepared in Example 5. In addition, the formation of micellar aggregates from the prepared polyrotaxane was verified using electron microscopy. FIG. 8 shows an electron micrograph of spherical micelle aggregates formed in an aqueous solution from the polyrotaxane prepared in Example 1.

The results of the Nile Red test and electron micrographs further support that polyrotaxane is suitable for micelle formation and material encapsulation.

Example 9
Drug Solubilization 10 mg of polyrotaxane from Example 6 was dissolved in 10 mL of HEPES buffered saline (pH = 7.2, NaCl concentration 0.9 wt.%). 24.4 mg of docetaxel (trade name: Taxotere) was dissolved in 5 ml of THF. Various amounts (20-200 μl) of docetaxel solution were added to 1 ml of the polyrotaxane solution and stirred for 16 hours. THF was evaporated. The residual mixture was passed through a 0.45 μm Teflon filter to give a clear filtrate. From the UV absorption of the filtrate at 229 nm, the concentration of dissolved docetaxel was determined in consideration of the absorption efficiency of docetaxel measured in ethanol 16240 Lmol ^-1 cm ^-1 . The concentration of the incorporated solubilized docetaxel is shown graphically in FIG.

Example 10
Formation of Ring Gel 10 mg of polystyrene-polyisoprene random copolymer polyrotaxane prepared in Example 2 and 1.5 μL (0.009 mmol) of hexamethylene disosocyanate cross-linking agent were dissolved in 0.1 mL of dichloromethane and transferred to a glass vial. .. The vial was shaken at room temperature for 10 minutes, transferred to a metal mold, sealed and heated to 80 ° C. The ring gel formed was washed with dichloromethane for 2 days and then with water for another day to remove unreacted polyrotaxane and cross-linking agent. After extraction, the gel was dried and the mass of the crosslinked white reticulum was measured.
Yield: 85%

The formation of the ring gel is graphically depicted in FIG.

Example 11
Polyrotaxan prepared via free radical polymerization: Poly (methylacrylate-co-styrene) -randomly methylated β-cyclodextrin polyrotaxane 2,2'-azobis [2- (2-imidazolin-2-yl) ) Propane] 9.20 mg (0.03 mmol) of dihydrochloride (radical initiator VA-044), 4.50 g (3.50 mmol) of randomly methylated β-cyclodextrin (RAMEB) and styrene (first 0.046 mL (0.45 mmol) of (monomer) was dissolved in 5 mL of deionized water and a stream of nitrogen gas was bubbled with stirring for 30 minutes. After the addition of 0.41 mL (0.39 g, 4.50 mmol) of freshly distilled methylacryllate (second monomer), the nitrogen flow was stopped and the system was agitated to allow homogeneous dissolution. .. The reaction vessel was heated to 35 ° C. and stirred for 3 days to initiate the reaction. The product was then filtered off and dried under vacuum at 45 ° C. overnight. A product (310 mg) with 5.9 wt.% Penetrated RAMEB and 4.7 wt.% Free RAMEB was obtained as a white precipitate.
^{1 1} H-NMR (CDCl ₃ , 400 MHz) δ / ppm = 3.50 (methoxy), 2.40-1.85 (methyl) and 1.80-1.10 ppm (methine) (poly (methylacrylate) ), 5.00 (H-1), 3.65 (H-7), 3.40 (H-8), 3.95-3.25 (H-2, H-3, H-4) , H-5, H-6) ppm (about RAMEB)
Optical rotation measurement (DMSO): c = 11.70 mg / mL, d = 0.1 dm, α = + 0.016 deg
ITC: Free RAMEB about 4.7wt%

FIG. 10 shows a ¹ H NMR spectrum of the polyrotaxane prepared in Example 11.

Example 12
Polyrotaxan Prepared Through Free Radical Polymerization: Poly (Dimethylbutadiene-co-PEG Methyl Ether Methrate) -Randomly Methyled β-Cyclodextrin Polyrotaxane 2,2'-Azobis [2- (2-Imidazoline-) 2-Il) Propane] dihydrochloride (radical initiator VA-044) 9.20 mg (0.03 mmol), randomly methylated β-cyclodextrin (RAMEB) 5.90 g (4.50 mmol) and poly (4.50 mmol). 0.21 g (0.45 mmol) of polyethylene glycol) methyl ether methacrylate (first monomer) was dissolved in 10 mL of deionized water and a stream of nitrogen gas was bubbled under stirring for 30 minutes. After the addition of 0.51 mL (0.37 g, 4.50 mmol) of freshly distilled dimethyl butadiene (second monomer), the nitrogen flow was stopped and the system was stirred to allow homogeneous dissolution. The reaction vessel was heated to 35 ° C. and stirred for 3 days to initiate the reaction. The product was then filtered off at 80 ° C., washed with water and dried under vacuum at 45 ° C. overnight. A product (570 mg) with 50 wt.% Penetrated RAMEB and no free RAMEB was obtained as a white precipitate.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0, no trace of free RAMEB
^{1 1} H-NMR (DMSO-d6, 400 MHz) δ / ppm = 2.10-1.35 (methylene) and 1.20-0.80 ppm (methyl) (for poly (dimethylbutadiene)), 5.00 (H-1), 3.65 (H-7), 3.40 (H-8), 3.95-3.25 (H-2, H-3, H-4, H-5, H- 6) ppm (about RAMEB)
Optical rotation measurement (DMSO): c = 10.05 mg / mL, d = 0.1 dm α = + 0.066 deg
ITC: Free RAMEB <1wt%

FIG. 11 shows a ¹ H NMR spectrum of the polyrotaxane prepared in Example 12.

Example 13
Polyrotaxane prepared via free radical polymerization: poly (isoprene-co-hydroxyethylmethacrylate) -β-cyclodextrin polyrotaxane 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride 9.20 mg (0.03 mmol) of salt (radical initiator VA-044), 5.1 g (4.5 mmol) of β-cyclodextrin, 0.055 mL (0.45 mmol) of hydroxyethyl-methacrylate (first monomer) Was dissolved in an 8M aqueous urea solution (total volume reached 25 mL) and the nitrogen gas stream was bubbled with stirring for 30 minutes. After the addition of 0.45 mL (0.31 g, 4.50 mmol) of freshly distilled isoprene (second monomer), the nitrogen flow was stopped and the system was stirred to allow homogeneous dissolution. The container was heated to 35 ° C. and stirred for 3 days. The reaction mixture was then heated to 90 ° C. for 30 minutes and filtered at 80 ° C. The residue was washed with warm water and 100 mL of water / 2-propanol 3: 1 (v / v) and dried under vacuum. The white solid was dissolved in 40 mL of DMSO, reprecipitated in 0.1 M aqueous NaCl solution, filtered off, washed with water and dried under vacuum. Polyrotaxane (820 mg) with 51.5 wt.% Penetrated cyclodextrin was obtained as a white solid. To determine free β-cyclodextrin, 7.53 mg of polyrotaxane was dissolved in 1.0 mL of DMSO, reprecipitated in 9.0 mL of 0.1 M NaCl aqueous solution and filtered. From the optical rotation of the clear filtrate α = + 0.008 deg (d = 1.0 dm), free β-cyclo assuming that the specific rotation of β-cyclodextrin is [α] _D = 157 deg mL g ^-1 dm ^-1 A dextrin content of 7 wt.% Was calculated.
^{1 1} H-NMR (DMSO-d6, 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 (methyl group) ) (About polyisoprene); 5.64-5.85 (m, 14H, OH-2, OH-3), 4.77-4.84 (H-1), 4.37-4.53 (OH) -6), 3.43-3.65 (H-3, H-5, H-6), 3.22-3.38 (H-2, H-4) ppm (for β-cyclodextrin)
Optical rotation measurement (DMSO): c = 5.58 mg / mL, d = 0.1 dm, α = + 0.049 deg

FIG. 12 shows a ¹ H NMR spectrum of the polyrotaxane prepared in Example 13.

Example 14
Polyrotaxane prepared via free radical polymerization: poly (isoprene-co-PEG methyl ether methacrylate) -hydroxypropyl-β-cyclodextrin polyrotaxane

Ammonium persulfate (radical initiator) 6.50 mg (0.03 mmol), hydroxypropyl-β-cyclodextrin (hereinafter referred to as "HP-β-CD", Wacker Chemie AG, CAVASOL® W7 HP, 5.0 g (3.33 mmol) of cyclic molecule and 0.17 g (0.33 mmol) of poly (ethylene glycol) methyl ether methacrylate (first monomer having a stopper group) were dissolved in 10 mL of deionized water, and then The system was bubbled with nitrogen gas for 30 minutes under stirring. After the addition of 0.33 mL (0.23 g, 3.33 mmol) of freshly distilled isoprene (second monomer, hydrophobic), the nitrogen flow was stopped and the system was stirred to give a homogeneous solution. (That is, HP-β-CD / isoprene complex formation). The reaction was initiated by the addition of a catalytic amount (0.08 mL) of N, N, N', N'-tetramethylethylenediamine (TMEDA) and stirred at room temperature for 48 hours. After the reaction, a clear aqueous solution was purified by ultrafiltration (polyether sulfone membrane, cutoff molecular weight 10 kDa). After lyophilization, a product (120 mg) with 54.5 wt.% Penetrated HP-β-CD and 4.5 wt.% Free HP-β-CD was obtained as a white powder.
TLC: R _f (EtOAc / MeOH 7/3 v / v) = 0, no trace of free HP β-CD
^{1 1} H-NMR (DMSO-d6, 400 MHz) δ / ppm = 5.15-4.95 (methine group), 2.05-1.85 (methylene group) and 1.75-1.45 ppm (methyl) Group) (for polyisoprene), 6.00-5.50 (m, OH), 5.01-4.60 (s, 1H, H-1), 4.50 (m, OH), 3.73 −3.25 (m, H-2, H-3, H-4, H-5, H-6, H-7, H-8), 1.02 (s, methyl group) ppm (HP β- About CD)
Optical rotation measurement: c = 3.60 mg / mL, d = 1 cm, α = 0.025 deg
ITC: Free HP β-CD 4.5wt%

FIG. 13 shows a ¹ H NMR spectrum of the polyrotaxane prepared in Example 14.

Claims (21)

(I)
At least (a) scan the first polymerizable monomer that having a topper group and, at least (b) a second polymerizable monomer, a step of performing a radical copolymerization, the second monomer is a cyclic molecules containing complexed by Ru process by providing a polyrotaxane,
During the copolymerization, a copolymer penetrating the cyclic molecule is formed, and during the copolymerization, the first monomer having a stopper group is incorporated at least partially between both ends of the chain of the copolymer. Moreover, the stopper group prevents the cyclic molecule from decomposing from the copolymer; and the amount of the first monomer having a stopper group is 0.1 mol% to 20 mol based on a total amount of 100 mol% of the polymerizable monomer. With the step of providing the polyrotaxane, which is% ;
(Ii)
A step of cross-linking the poly-rotaxane, which comprises a step of intermolecularly cross-linking the poly-rotaxane by cross-linking the cyclic molecule with a cross-linking agent;
A method of preparing a crosslinked polyrotaxane, comprising: The step of providing the polyrotaxane is
(A) providing a composition comprising a first polymerizable monomer having a cyclic molecule and a stopper group;
(B) forming a complex with a second polymerizable monomer combined with the composition of step (a) step and the cyclic molecule and the second monomer;
Comprises; was performed to free-radical copolymerization of the composition of step (c) (b), forming a polyrotaxane
A random copolymer penetrating the cyclic molecule is formed during the copolymerization, and the first monomer having a stopper group is randomly incorporated along the chain of the copolymer during the copolymerization. The method described in. The method according to claim 1, wherein the amount of the first monomer having a stopper group is 0.5 mol% to 18 mol% based on the total amount of the polymerizable monomer of 100 mol%. The step of providing the polyrotaxane is
(A) providing a composition comprising a first polymerizable monomer having a stopper group;
(B) step is carried out radical polymerization of the composition of (a), forming a block A comprising repeating units derived from the first monomer having a stopper group;
(C) A step of radically copolymerizing the second polymerizable monomer with the block A to form a block B containing a repeating unit derived from the second polymerizable monomer attached to the block A. Te, the second monomer is complexed by the cyclic molecule, and steps;
(D) A step of radically copolymerizing a third polymerizable monomer having a stopper group on the block B to form a block C, wherein the third monomer is the same as or different from the first monomer. Including the process and;
During the copolymerization, an ABC block copolymer is formed, the cyclic molecule is passed over block B, and block B is placed between block A and block C; and said first having a stopper group. The method according to claim 1, wherein the total amount of one monomer and the third monomer is 0.1 mol% to 20 mol% based on a total amount of 100 mol% of polymerizable monomers. The method of claim 2, wherein the composition provided in step (a) comprises a radical initiator or polymerization is accelerated by the addition of a radical initiator accelerator. The method of claim 1, wherein the cyclic molecule is selected from the group consisting of cyclodextrins, cyclodextrin derivatives and any combination thereof. The method according to claim 1, wherein the first monomer has a molecular weight of 70 g / mol to 1000 g / mol. The first monomer having a stopper group is milsen, aromatic vinyl monomer, N-isopropyl (meth) acrylamide, N-vinylcaprolactam, N-vinylimidazole, poly (ethylene glycol) (meth) acrylate, α, ω-. The first monomer selected from the group consisting of bis (meth) acrylate and any combination thereof or having a stopper group is a styrene optionally substituted, a styrene sulfonic acid optionally substituted. The method according to claim 1, wherein the method is selected from the group consisting of optionally substituted vinylpyridine, optionally substituted divinylbenzene, and any combination thereof. The second monomer is a nonionic monomer, or the second monomer is 1,3-diene, 1,3,5-triene, (meth) acrylate, vinyl ester (eg, vinyl acetate). , Vinyl-ether, (meth) acrylonitrile, (meth) acrylic acid, (meth) acrylamide, and any combination thereof, selected from the group of vinyl monomers having a molecular weight of less than 120 g / mol, claim 1. The method described in. Whether the copolymerization is carried out in an aqueous medium
The method of claim 1, wherein the copolymerization is carried out using a water-soluble radical initiator, or the copolymerization is carried out using a chain transfer agent. Polyrotaxane comprising a benzalkonium polymer to penetrate the cyclic molecules and the ring-shaped molecules, via said cyclic molecule and a crosslinking agent are intermolecular crosslinking, a crosslinked polyrotaxane,
Non said copolymer, containing a structural unit derived from a first polymerizable monomer that having a least (a) scan Topper group, and structural units derived from at least (b) a second polymerizable monomer, a The structural unit, which is an ionic copolymer and is derived from a first monomer having a stopper group, is at least partially incorporated between both ends of the chain of the copolymer, and the stopper group decomposes the cyclic compound from the copolymer. A crosslinked polyrotaxane in which the amount of the structural unit derived from the first monomer having a stopper group is 0.1 mol% to 20 mol% based on 100 mol% of the total structural unit of the copolymer. The copolymer is a random copolymer in which the structural units derived from the first polymerizable monomer having a stopper group are at least partially randomly incorporated along the strands of the copolymer between its ends. The crosslinked polyrotaxane according to claim 11. The crosslinked polyrotaxane according to claim 11, wherein the amount of the structural unit derived from the first monomer having a stopper group is 0.5 mol% to 18 mol% based on 100 mol% of the total structural unit of the copolymer. The copolymer contains a block A containing a repeating unit derived from the first polymerizable monomer having a stopper group, a block B containing a repeating unit derived from the second polymerizable monomer, and a third polymerization. A block copolymer containing a block C containing a repeating unit derived from a sex monomer, wherein the repeating unit derived from the third monomer is the same as or different from the repeating unit derived from the first monomer. In the block copolymer, the block B is placed between the block A and the block C, the cyclic molecule is passed over the block B, and the structural unit and derived from the first monomer. The crosslinked polyrotaxane according to claim 11, wherein the total amount of the structural units derived from the third monomer is 0.1 mol% to 20 mol% based on 100 mol% of the total structural units of the copolymer. .. The crosslinked polyrotaxan according to claim 11, wherein the cyclic molecule is selected from the group consisting of cyclodextrin, cyclodextrin derivatives and any combination thereof. The crosslinked polyrotaxane according to claim 11, wherein the first monomer has a molecular weight of 70 g / mol to 1000 g / mol. The first monomer having a stopper group is milsen, aromatic vinyl monomer, N-isopropyl (meth) acrylamide, N-vinylcaprolactam, N-vinylimidazole, poly (ethylene glycol) (meth) acrylate, α, ω-. The first monomer selected from the group consisting of bis (meth) acrylate and any combination thereof or having a stopper group is styrene which may be substituted, styrene sulfonic acid which may be substituted. The crosslinked polyrotaxan according to claim 11, which is selected from the group consisting of optionally substituted vinylpyridine, optionally substituted divinylbenzene, and any combination thereof. The second monomer is a hydrophobic monomer, or the second monomer is 1,3-diene, 1,3,5-triene, (meth) acrylate, vinyl ester (eg, vinyl acetate), vinyl. 10. According to claim 11, selected from the group of vinyl monomers having a molecular weight of less than 120 g / mol, consisting of ether, (meth) acrylonitrile, (meth) acrylic acid , (meth) acrylamide, and any combination thereof. Cross-linked polyrotaxane. The intermolecular cross-linking of polyrotaxane is provided by a covalent bond between the first cyclic molecule threaded over the first copolymer chain and the second cyclic molecule threaded over the second copolymer chain. The crosslinked polyrotaxane according to claim 11 . Before SL crosslinking agent, diisocyanate, blocked diisocyanate, diisothiocyanate, bis-epoxide, cyanuric chloride, divinyl sulfone, and is selected from the group consisting of any combination thereof, as claimed in claim 11 Cross-linked polyrotaxane. A dispersion containing metal particles and / or metal oxide particles and the crosslinked polyrotaxane according to claim 11.